<\/strong><\/span><\/h4>\n<\/strong><\/span><\/h4>\n<\/strong><\/span><\/h4>\n<\/strong><\/span><\/h4>\nDr.\u00a0Costache\u00a0Daniel<\/strong><\/span>
Spitalul Universitar de Urgen\u0163\u0103 Militar Central “Dr. Carol Davila\u201d<\/strong><\/span><\/h4>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”3.19.14″][et_pb_column type=”4_4″ _builder_version=”3.19.14″][et_pb_text _builder_version=”3.19.18″]<\/p>\n
Exist\u0103 o leg\u0103tur\u0103 \u00eentre terapia biologic\u0103 \u00een psoriazis \u0219i cancerul de organ?<\/span>
Autori: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache<\/span><\/p>\nLa baza terapiilor moderne se afl\u0103 doi piloni fundamentali, anume pe de o parte studiile clinice cu num\u0103r semnificativ de pacien\u0163i, \u015fi pe de alt\u0103 parte experien\u0163a clinic\u0103 acumulat\u0103 pe milioane de pacien\u0163i.
Prin \u00eensumarea acestor doi factori fundamentali se ob\u021bin rezultate complexe, nu \u00eentotdeauna congruente, dar care permit s\u0103 analiz\u0103m \u00een termeni c\u00e2t se poate de obiectivi at\u00e2t eficacitatea tratamentului, c\u00e2t \u015fi siguran\u0163a produselor farmacologice utilizate \u015fi, nu \u00een ultimul r\u00e2nd, profilul pacien\u0163ilor candida\u0163i pentru tratament.
Exist\u0103 frecvent asocieri sau favoriz\u0103ri patologice \u00een afec\u0163iuni precum psoriazis vulgar sau boala Crohn. Ast\u0103zi, nimeni nu se mai mir\u0103 atunci c\u00e2nd constat\u0103 la un pacient psoriatic coexisten\u0163a sindromului metabolic, a afec\u0163iunilor intestinale inflamatorii, depresiei sau afec\u0163iunilor cardiace inflamatorii, punctul comun al acestora fiind inflama\u0163ia necontrolat\u0103 sistemic\u0103 declan\u015fat\u0103 de o cauz\u0103 necunoscut\u0103.
\u015etiut\u0103 fiind implicarea sistemului inflamator \u00een controlul multiplic\u0103rii celulare \u00een organism, discu\u0163ia despre corela\u0163iile \u00eentre sindromul inflamator cronic sistemic \u015fi tumorile hematologice sau de organ este absolut fireasc\u0103. Exist\u0103 numeroase dovezi referitoare la rolul \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale, fiind \u00een prezent definite cel pu\u0163in \u015fase aspecte caracteristice care ofer\u0103 celulelor avantaje de supravie\u0163uire in vivo. Aceste aspecte sunt: promovarea unor semnale autocrine de cre\u015ftere celular\u0103, instalarea insensibilit\u0103\u0163ii la semnalele anti-cre\u015ftere, favorizarea angiogenezei, evitarea c\u0103ilor apoptozei, favorizarea mecanismelor de invazivitate tisular\u0103 \u015fi de metastazare, replicarea celular\u0103 nerestric\u0163ionat\u0103.
Numeroase studii dovedesc implicarea \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale.
Tabelul 1: \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale
– produc\u0163ie de NO (alter\u0103ri ale ADN, promovare tumoral\u0103 cGMP mediat\u0103)
– cre\u015ftere autocrin\u0103 \u015fi factor de supravie\u0163uire pentru celule maligne
– activarea E6\/E7 ARNm \u00een celulele infectate cu HPV
– activarea Src kinazei
– remodelare tisular\u0103 prin matrix metaloproteinaze
– controlul infiltr\u0103rii leucocitare prin modulare citokinic\u0103
– inhibarea E-caderinei, cre\u015ftere nucleolar\u0103 de b catenin\u0103
– cre\u015fterea motilit\u0103\u0163ii (invazivit\u0103\u0163ii) tumorale
– tranzi\u0163ie epitelial-mezenchimal\u0103
– induc\u0163ie de factori angiogenici
– pierderea r\u0103spunsului la androgeni
– rezisten\u0163\u0103 la medica\u0163ie citotoxic\u0103
Datorit\u0103 acestor efecte deosebit de complexe \u015fi de complementare \u00een acela\u015fi timp, care arat\u0103 dincolo de orice comentarii c\u0103 organismul este posesorul unei balan\u0163e extrem de bine reglat\u0103 \u00een privin\u0163a mecanismelor sale inflamatorii de ap\u0103rare antitumoral\u0103, un tratament imunomodulator care s\u0103 influen\u0163eze titrurile circulante \u015fi tisulare de TNF poate pe drept cuv\u00e2nt s\u0103 ridice semne de \u00eentrebare \u015fi \u00eengrijor\u0103ri.
Tabelul 2: \u03b1-TNF \u00een combaterea neoplaziei
– injectarea de TNF intratumoral \u2013 oprirea fluxului sanguin, hemoragii intratumorale, necroz\u0103 vascular\u0103
– colonizare tumoral\u0103 cu PMN
– inhibarea cre\u015fterii tumorale prin macrofage \u015fi celule NK (Blankenstein, 1991)
– distruc\u0163ie \u015fi rejec\u0163ie tumoral\u0103 NK \u015fi LAK induse (Baxevanis, 2000)
– imunitate antitumoral\u0103 \u015fi eliminarea CTL indus\u0103 a tumorilor
– favorizarea apoptozei citocrom c mitocondrial indus\u0103
– apoptoz\u0103 c-myc dependent\u0103
– inhibarea activ\u0103rii NF-kB
Studiile clinice efectuate, metaanalizele, datele din registrele interna\u0163ionale, dar \u015fi, nu \u00een ultimul r\u00e2nd, experien\u0163a clinic\u0103 a speciali\u015ftilor sunt instrumentele puternice pe care le avem la \u00eendem\u00e2n\u0103 atunci c\u00e2nd facem afirma\u0163ia c\u0103 p\u00e2n\u0103 la acest moment nu exist\u0103 niciun fel de date care s\u0103 arate c\u0103 terapiile anti \u03b1-TNF ar fi incriminate \u00een induc\u0163ia neoplaziilor, fie ele de organ sau hematologice. Preocup\u0103rile ini\u0163iale care legau terapia biologic\u0103 de dezvoltarea limfoamelor par, \u00een lumina informa\u0163iilor actuale, desuete.
Cu toate acestea, ar fi o dovad\u0103 de iresponsabilitate s\u0103 nu admitem c\u0103 terapia biologic\u0103, ca toate formulele terapeutice cu un grad de imunosupresie de altfel, nu ar putea s\u0103 favorizeze dezvoltarea unei neoplazii, fie preexistent\u0103 fie de novo. Prin tulburarea balan\u0163ei mai sus prezentat\u0103 sumar, terapiile biologice anti \u03b1-TNF pot ajuta \u00eentr-o m\u0103sur\u0103 impredictibil\u0103 evitarea supravegherii imune de c\u0103tre neoplaziile existente la momentul ini\u0163ierii tratamentului, dar insuficient dezvoltate pentru a fi depistate cu metodele disponibile \u00een prezent.
Supravegherea vigilent\u0103 post marketing a produselor medicamentoase este vital\u0103, datorit\u0103 circumstan\u0163elor studiilor clinice, care fac s\u0103 se ajung\u0103 la situa\u0163ia c\u0103 \u00een practica curent\u0103 se utilizeaz\u0103 medicamente inclusiv la categorii de pacien\u0163i care au fost exclu\u015fi explicit \u00een studiile clinice \u015fi fa\u0163\u0103 de care \u00een consecin\u0163\u0103 datele privind siguran\u0163a sunt relativ incomplete, dac\u0103 exist\u0103 c\u00e2t de c\u00e2t. Metaanalizele suplinesc o serie din aceste dezavantaje ale studiilor clinice, \u00een primul r\u00e2nd num\u0103rul limitat de pacien\u0163i. Durata de expunere individual\u0103 la moleculele active \u00eens\u0103 nu se modific\u0103, de\u015fi datele sunt comunicate sub form\u0103 statistic\u0103 de tip pacient-ani de expunere…
O metaanaliz\u0103 pe 9 studii clinice arat\u0103 un risc de 3 ori mai mare (OR 3,3 cu CI 95%) de a dezvolta o malignitate la pacien\u0163ii trata\u0163i cu anti \u03b1-TNF fa\u0163\u0103 de martor, riscul fiind propor\u0163ional cu doza administrat\u0103. Nota bene, \u00een studiul men\u0163ionat rata de neoplazii \u00een bra\u0163ul de control a fost anormal de sc\u0103zut\u0103…
Pentru a ilustra aceast\u0103 realitate prezent\u0103m un caz clinic, ilustrativ pentru riscurile la care sunt expu\u015fi \u00een acela\u015fi timp \u015fi pacien\u0163ii dar \u015fi medicii, \u00een ciuda bunei credin\u0163e a ambilor.<\/p>\n
Is there a link between biological therapy in psoriasis and organ cancer?<\/span>
Authors: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache<\/span><\/p>\nAt the basis of modern therapies there are two fundamental pillars, namely the clinical trials with a significant number of patients on one hand and the clinical experience accumulated on millions of patients on the other hand.
By summing up these two fundamental factors we obtain complex results, not always congruent, but which allow us to analyze in objective terms both the efficacy of the treatment and the safety of the pharmacological products used and, last but not least, the profile of the candidates for treatment.
There is often a bias association or pathological conditions such as vulgar psoriasis or Crohn’s disease. Today no one is surprised to find out to a psoriatic patient the coexistence of metabolic syndrome, inflammatory bowel disease, depression or inflammatory heart disease, their common point being the uncontrolled systemic inflammation triggered by an unknown cause.
Knowing the involvement of the inflammatory system in the control of cellular multiplication in the body, the discussion about the correlations between chronic systemic inflammatory syndrome and hematological or organ tumors is absolutely natural. There is ample evidence on the role of TNF-\u03b1 in regulating tumor promotion and propagation and at least six characteristic aspects are currently set offering advantages to cells for in vivo survival. These aspects are: promoting autocrine cell growth signals, installing insensitivity to anti-growth signals, favoring angiogenesis, avoiding apoptosis pathways, favoring tissue and metastasis invasiveness mechanisms, unrestricted cellular replication.
Numerous studies prove the involvement of TNF-\u03b1 in regulating tumor promotion and propagation.
Table 1: TNF-\u03b1 in the regulation of tumor promotion and propagation
– production of NO (DNA alterations, mediated cGMP tumor promotion)
– autocrine growth and survival factor for malignant cells
– activation of E6 \/ E7 mRNA in HPV-infected cells
– activation of Src kinase
– tissue remodeling by matrix metalloproteinases
– control of leukocyte infiltration by cytokine modulation
– inhibition of E-cadherin, nucleolar growth of b catenin
– increased tumor motility (invasiveness)
– epithelial-mesenchymal transition
– induction of angiogenic factors
– loss of androgen response
– resistance to cytotoxic medication
Because of these particularly complex and complementary effects at the same time which shows beyond any comments that the body has very well-balanced scales regarding its inflammatory mechanisms of antitumor defense, an immunomodulatory treatment to influence circulating and tissue titres of TNF can rightly raise questions and concerns.
Table 2: TNF-\u03b1 in counteracting neoplasia
– intratumoral TNF injection – blood flow stop, intratumoral haemorrhage, vascular necrosis
– PMN tumor colonization
– inhibition of tumor growth by macrophages and NK cells (Blankenstein, 1991)
– NK and LAK induced tumor destruction and rejection (Baxevanis, 2000)
– antitumor immunity and elimination of tumor-induced CTL
– favoring induced cytochrome c mitochondrial apoptosis
– c-myc dependent apoptosis
– inhibition of NF-\u03baB activation
Clinical trials, meta-analyzes, data from international registries and last but not least the clinical experience of specialists are the powerful tools we have at hand when we assert that there is no data to date that anti-\u03b1-TNF therapies would be incriminated in the induction of neoplasia whether organ or hematologic. The initial concerns that linked biological therapy to the development of lymphomas appear in the light of current information as obsolete.
However, it would be irresponsible not to admit that biological therapy, like all other immunosuppressed therapeutic formulas, could not favor the development of a pre-existing or de novo neoplasm. By analyzing the above-mentioned balance disorder, anti-\u03b1-TNF biological therapies may, to an unpredictable extent, help to avoid immune surveillance by existing neoplasms at the time of initiation but insufficiently developed to detect with the currently available methods.
The vigilant post-marketing surveillance of medicinal products is vital, due to the circumstances of clinical trials, which make it possible to find that in current practice medication is also used in categories of patients explicitly excluded in clinical trials and, therefore, data on safety are relatively incomplete, if any at all. Meta-analyzes support a number of these disadvantages of clinical trials, primarily the limited number of patients. However, the duration of individual exposure to active molecules does not change, although data are reported in the patient-years of statistical form type of exposure…
A meta-analysis of 9 clinical trials shows a 3-fold higher risk (OR 3.3 with 95% CI) to develop malignancy in anti-\u03b1-TNF-treated patients compared to the control, the risk being proportional to the dose administered. NB, the rate of cancer in the study mentioned in the control arm was abnormally low…
To illustrate this reality we present a clinical case illustrative for the risks to both patients and physicians, despite the good faith of both.<\/p>\n
Scurt CV<\/span><\/p>\nMedic primar dermatovenerologie
Doctor \u00een \u015ftiin\u0163e medicale – Studiul microcircula\u0163iei sanguine \u00een patologia cutanat\u0103.
Coordonator activitate de cercetare, studii clinice la Spitalul Universitar de Urgen\u0163\u0103 Militar Central \u201eDr. Carol Davila\u201d, Bucure\u015fti.
Editor executiv, Romanian Journal of Military Medicine, revist\u0103 editat\u0103 de Asocia\u0163ia Medicilor \u015fi Farmaci\u015ftilor Militari din Rom\u00e2nia, Universitatea de Medicin\u0103 \u015fi Farmacie “Carol Davila” Bucure\u0219ti.
Delegat Ministerul Ap\u0103r\u0103rii Na\u0163ionale \u00een Consiliul Na\u0163ional al Colegiului Medicilor din Rom\u00e2nia.
Activitate clinic\u0103 \u015fi de cercetare \u00een cadrul departamentului de Dermatologie al Spitalului Universitar de Urgen\u0163\u0103 Militar Central \u201dDr. Carol Davila\u201d, Bucure\u015fti.
Competen\u0163\u0103 \u00een evaluarea microcircula\u0163iei.
Competen\u0163\u0103 \u00een electrochirurgie \u015fi laser chirurgie \u00een dermatologie.
Formator de formatori \u00een dermatocosmetologie.<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”3.19.4″ background_color=”rgba(117,194,33,0.23)” background_image=”https:\/\/pdi.ro\/2019\/wp-content\/uploads\/2019\/01\/back_justflowers_overlay1.png” background_blend=”luminosity” custom_padding=”54px|0px|0|0px|false|false” top_divider_style=”waves2″ top_divider_color=”#ffffff” top_divider_height=”155px” bottom_divider_style=”waves2″ bottom_divider_color=”#75c221″ bottom_divider_flip=”vertical”][et_pb_row custom_padding=”61px|0px|69px|0px|false|false” _builder_version=”3.18.9″][et_pb_column type=”3_5″ _builder_version=”3.18.9″][et_pb_text _builder_version=”3.19.4″ text_font=”Kaushan Script||||||||” text_text_color=”#f0622a” text_font_size=”30px” header_font=”||||||||” background_layout=”dark”]<\/p>\n
Contacteaz\u0103 operatorul PDI 2019<\/p>\n
[\/et_pb_text][et_pb_contact_form email=”contact@pdi.ro\/2019″ submit_button_text=”Trimite mesajul” _builder_version=”3.19.4″ title_font=”||||||||”][et_pb_contact_field field_id=”Name” field_title=”Nume” _builder_version=”3.18.9″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][et_pb_contact_field field_id=”Email” field_title=”Adresa de e-mail” field_type=”email” _builder_version=”3.19.4″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][et_pb_contact_field field_id=”Message” field_title=”Mesajul dvs.” field_type=”text” fullwidth_field=”on” _builder_version=”3.18.9″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][\/et_pb_contact_form][\/et_pb_column][et_pb_column type=”2_5″ _builder_version=”3.18.9″][et_pb_text _builder_version=”3.19.4″ text_font=”Kaushan Script||||||||” text_text_color=”#f0622a” text_font_size=”30px” header_font=”||||||||” background_layout=”dark”]<\/p>\n
Operatorul PDI 2019<\/p>\n
[\/et_pb_text][et_pb_text _builder_version=”3.19.4″ text_font=”||||||||”]![\"\"](\"https:\/\/pdi.ro\/2019\/wp-content\/uploads\/2019\/01\/eventer_logo_150px.png\")
<\/span><\/p>\n<\/span><\/p>\n<\/span><\/p>\nAdresa: Str. A. Panu nr. 13, Iasi<\/span>
\nTel.: 0332.40.88.00-05<\/span>
\nE-mail: inscrieri@pdi.ro\/2019<\/a>
\n<\/span>Website:\u00a0<\/span>www.eventernet.ro<\/a>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"Dr.\u00a0Costache\u00a0Daniel Spitalul Universitar de Urgen\u0163\u0103 Militar Central “Dr. Carol Davila\u201dExist\u0103 o leg\u0103tur\u0103 \u00eentre terapia biologic\u0103 \u00een psoriazis \u0219i cancerul de organ? Autori: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache La baza terapiilor moderne se afl\u0103 doi piloni fundamentali, anume pe de o parte studiile clinice cu num\u0103r semnificativ de pacien\u0163i, \u015fi pe de […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"class_list":["post-4091","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/comments?post=4091"}],"version-history":[{"count":8,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091\/revisions"}],"predecessor-version":[{"id":4726,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091\/revisions\/4726"}],"wp:attachment":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/media?parent=4091"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
<\/strong><\/span><\/h4>\n<\/strong><\/span><\/h4>\nDr.\u00a0Costache\u00a0Daniel<\/strong><\/span>
Spitalul Universitar de Urgen\u0163\u0103 Militar Central “Dr. Carol Davila\u201d<\/strong><\/span><\/h4>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”3.19.14″][et_pb_column type=”4_4″ _builder_version=”3.19.14″][et_pb_text _builder_version=”3.19.18″]<\/p>\n
Exist\u0103 o leg\u0103tur\u0103 \u00eentre terapia biologic\u0103 \u00een psoriazis \u0219i cancerul de organ?<\/span>
Autori: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache<\/span><\/p>\nLa baza terapiilor moderne se afl\u0103 doi piloni fundamentali, anume pe de o parte studiile clinice cu num\u0103r semnificativ de pacien\u0163i, \u015fi pe de alt\u0103 parte experien\u0163a clinic\u0103 acumulat\u0103 pe milioane de pacien\u0163i.
Prin \u00eensumarea acestor doi factori fundamentali se ob\u021bin rezultate complexe, nu \u00eentotdeauna congruente, dar care permit s\u0103 analiz\u0103m \u00een termeni c\u00e2t se poate de obiectivi at\u00e2t eficacitatea tratamentului, c\u00e2t \u015fi siguran\u0163a produselor farmacologice utilizate \u015fi, nu \u00een ultimul r\u00e2nd, profilul pacien\u0163ilor candida\u0163i pentru tratament.
Exist\u0103 frecvent asocieri sau favoriz\u0103ri patologice \u00een afec\u0163iuni precum psoriazis vulgar sau boala Crohn. Ast\u0103zi, nimeni nu se mai mir\u0103 atunci c\u00e2nd constat\u0103 la un pacient psoriatic coexisten\u0163a sindromului metabolic, a afec\u0163iunilor intestinale inflamatorii, depresiei sau afec\u0163iunilor cardiace inflamatorii, punctul comun al acestora fiind inflama\u0163ia necontrolat\u0103 sistemic\u0103 declan\u015fat\u0103 de o cauz\u0103 necunoscut\u0103.
\u015etiut\u0103 fiind implicarea sistemului inflamator \u00een controlul multiplic\u0103rii celulare \u00een organism, discu\u0163ia despre corela\u0163iile \u00eentre sindromul inflamator cronic sistemic \u015fi tumorile hematologice sau de organ este absolut fireasc\u0103. Exist\u0103 numeroase dovezi referitoare la rolul \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale, fiind \u00een prezent definite cel pu\u0163in \u015fase aspecte caracteristice care ofer\u0103 celulelor avantaje de supravie\u0163uire in vivo. Aceste aspecte sunt: promovarea unor semnale autocrine de cre\u015ftere celular\u0103, instalarea insensibilit\u0103\u0163ii la semnalele anti-cre\u015ftere, favorizarea angiogenezei, evitarea c\u0103ilor apoptozei, favorizarea mecanismelor de invazivitate tisular\u0103 \u015fi de metastazare, replicarea celular\u0103 nerestric\u0163ionat\u0103.
Numeroase studii dovedesc implicarea \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale.
Tabelul 1: \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale
– produc\u0163ie de NO (alter\u0103ri ale ADN, promovare tumoral\u0103 cGMP mediat\u0103)
– cre\u015ftere autocrin\u0103 \u015fi factor de supravie\u0163uire pentru celule maligne
– activarea E6\/E7 ARNm \u00een celulele infectate cu HPV
– activarea Src kinazei
– remodelare tisular\u0103 prin matrix metaloproteinaze
– controlul infiltr\u0103rii leucocitare prin modulare citokinic\u0103
– inhibarea E-caderinei, cre\u015ftere nucleolar\u0103 de b catenin\u0103
– cre\u015fterea motilit\u0103\u0163ii (invazivit\u0103\u0163ii) tumorale
– tranzi\u0163ie epitelial-mezenchimal\u0103
– induc\u0163ie de factori angiogenici
– pierderea r\u0103spunsului la androgeni
– rezisten\u0163\u0103 la medica\u0163ie citotoxic\u0103
Datorit\u0103 acestor efecte deosebit de complexe \u015fi de complementare \u00een acela\u015fi timp, care arat\u0103 dincolo de orice comentarii c\u0103 organismul este posesorul unei balan\u0163e extrem de bine reglat\u0103 \u00een privin\u0163a mecanismelor sale inflamatorii de ap\u0103rare antitumoral\u0103, un tratament imunomodulator care s\u0103 influen\u0163eze titrurile circulante \u015fi tisulare de TNF poate pe drept cuv\u00e2nt s\u0103 ridice semne de \u00eentrebare \u015fi \u00eengrijor\u0103ri.
Tabelul 2: \u03b1-TNF \u00een combaterea neoplaziei
– injectarea de TNF intratumoral \u2013 oprirea fluxului sanguin, hemoragii intratumorale, necroz\u0103 vascular\u0103
– colonizare tumoral\u0103 cu PMN
– inhibarea cre\u015fterii tumorale prin macrofage \u015fi celule NK (Blankenstein, 1991)
– distruc\u0163ie \u015fi rejec\u0163ie tumoral\u0103 NK \u015fi LAK induse (Baxevanis, 2000)
– imunitate antitumoral\u0103 \u015fi eliminarea CTL indus\u0103 a tumorilor
– favorizarea apoptozei citocrom c mitocondrial indus\u0103
– apoptoz\u0103 c-myc dependent\u0103
– inhibarea activ\u0103rii NF-kB
Studiile clinice efectuate, metaanalizele, datele din registrele interna\u0163ionale, dar \u015fi, nu \u00een ultimul r\u00e2nd, experien\u0163a clinic\u0103 a speciali\u015ftilor sunt instrumentele puternice pe care le avem la \u00eendem\u00e2n\u0103 atunci c\u00e2nd facem afirma\u0163ia c\u0103 p\u00e2n\u0103 la acest moment nu exist\u0103 niciun fel de date care s\u0103 arate c\u0103 terapiile anti \u03b1-TNF ar fi incriminate \u00een induc\u0163ia neoplaziilor, fie ele de organ sau hematologice. Preocup\u0103rile ini\u0163iale care legau terapia biologic\u0103 de dezvoltarea limfoamelor par, \u00een lumina informa\u0163iilor actuale, desuete.
Cu toate acestea, ar fi o dovad\u0103 de iresponsabilitate s\u0103 nu admitem c\u0103 terapia biologic\u0103, ca toate formulele terapeutice cu un grad de imunosupresie de altfel, nu ar putea s\u0103 favorizeze dezvoltarea unei neoplazii, fie preexistent\u0103 fie de novo. Prin tulburarea balan\u0163ei mai sus prezentat\u0103 sumar, terapiile biologice anti \u03b1-TNF pot ajuta \u00eentr-o m\u0103sur\u0103 impredictibil\u0103 evitarea supravegherii imune de c\u0103tre neoplaziile existente la momentul ini\u0163ierii tratamentului, dar insuficient dezvoltate pentru a fi depistate cu metodele disponibile \u00een prezent.
Supravegherea vigilent\u0103 post marketing a produselor medicamentoase este vital\u0103, datorit\u0103 circumstan\u0163elor studiilor clinice, care fac s\u0103 se ajung\u0103 la situa\u0163ia c\u0103 \u00een practica curent\u0103 se utilizeaz\u0103 medicamente inclusiv la categorii de pacien\u0163i care au fost exclu\u015fi explicit \u00een studiile clinice \u015fi fa\u0163\u0103 de care \u00een consecin\u0163\u0103 datele privind siguran\u0163a sunt relativ incomplete, dac\u0103 exist\u0103 c\u00e2t de c\u00e2t. Metaanalizele suplinesc o serie din aceste dezavantaje ale studiilor clinice, \u00een primul r\u00e2nd num\u0103rul limitat de pacien\u0163i. Durata de expunere individual\u0103 la moleculele active \u00eens\u0103 nu se modific\u0103, de\u015fi datele sunt comunicate sub form\u0103 statistic\u0103 de tip pacient-ani de expunere…
O metaanaliz\u0103 pe 9 studii clinice arat\u0103 un risc de 3 ori mai mare (OR 3,3 cu CI 95%) de a dezvolta o malignitate la pacien\u0163ii trata\u0163i cu anti \u03b1-TNF fa\u0163\u0103 de martor, riscul fiind propor\u0163ional cu doza administrat\u0103. Nota bene, \u00een studiul men\u0163ionat rata de neoplazii \u00een bra\u0163ul de control a fost anormal de sc\u0103zut\u0103…
Pentru a ilustra aceast\u0103 realitate prezent\u0103m un caz clinic, ilustrativ pentru riscurile la care sunt expu\u015fi \u00een acela\u015fi timp \u015fi pacien\u0163ii dar \u015fi medicii, \u00een ciuda bunei credin\u0163e a ambilor.<\/p>\n
Is there a link between biological therapy in psoriasis and organ cancer?<\/span>
Authors: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache<\/span><\/p>\nAt the basis of modern therapies there are two fundamental pillars, namely the clinical trials with a significant number of patients on one hand and the clinical experience accumulated on millions of patients on the other hand.
By summing up these two fundamental factors we obtain complex results, not always congruent, but which allow us to analyze in objective terms both the efficacy of the treatment and the safety of the pharmacological products used and, last but not least, the profile of the candidates for treatment.
There is often a bias association or pathological conditions such as vulgar psoriasis or Crohn’s disease. Today no one is surprised to find out to a psoriatic patient the coexistence of metabolic syndrome, inflammatory bowel disease, depression or inflammatory heart disease, their common point being the uncontrolled systemic inflammation triggered by an unknown cause.
Knowing the involvement of the inflammatory system in the control of cellular multiplication in the body, the discussion about the correlations between chronic systemic inflammatory syndrome and hematological or organ tumors is absolutely natural. There is ample evidence on the role of TNF-\u03b1 in regulating tumor promotion and propagation and at least six characteristic aspects are currently set offering advantages to cells for in vivo survival. These aspects are: promoting autocrine cell growth signals, installing insensitivity to anti-growth signals, favoring angiogenesis, avoiding apoptosis pathways, favoring tissue and metastasis invasiveness mechanisms, unrestricted cellular replication.
Numerous studies prove the involvement of TNF-\u03b1 in regulating tumor promotion and propagation.
Table 1: TNF-\u03b1 in the regulation of tumor promotion and propagation
– production of NO (DNA alterations, mediated cGMP tumor promotion)
– autocrine growth and survival factor for malignant cells
– activation of E6 \/ E7 mRNA in HPV-infected cells
– activation of Src kinase
– tissue remodeling by matrix metalloproteinases
– control of leukocyte infiltration by cytokine modulation
– inhibition of E-cadherin, nucleolar growth of b catenin
– increased tumor motility (invasiveness)
– epithelial-mesenchymal transition
– induction of angiogenic factors
– loss of androgen response
– resistance to cytotoxic medication
Because of these particularly complex and complementary effects at the same time which shows beyond any comments that the body has very well-balanced scales regarding its inflammatory mechanisms of antitumor defense, an immunomodulatory treatment to influence circulating and tissue titres of TNF can rightly raise questions and concerns.
Table 2: TNF-\u03b1 in counteracting neoplasia
– intratumoral TNF injection – blood flow stop, intratumoral haemorrhage, vascular necrosis
– PMN tumor colonization
– inhibition of tumor growth by macrophages and NK cells (Blankenstein, 1991)
– NK and LAK induced tumor destruction and rejection (Baxevanis, 2000)
– antitumor immunity and elimination of tumor-induced CTL
– favoring induced cytochrome c mitochondrial apoptosis
– c-myc dependent apoptosis
– inhibition of NF-\u03baB activation
Clinical trials, meta-analyzes, data from international registries and last but not least the clinical experience of specialists are the powerful tools we have at hand when we assert that there is no data to date that anti-\u03b1-TNF therapies would be incriminated in the induction of neoplasia whether organ or hematologic. The initial concerns that linked biological therapy to the development of lymphomas appear in the light of current information as obsolete.
However, it would be irresponsible not to admit that biological therapy, like all other immunosuppressed therapeutic formulas, could not favor the development of a pre-existing or de novo neoplasm. By analyzing the above-mentioned balance disorder, anti-\u03b1-TNF biological therapies may, to an unpredictable extent, help to avoid immune surveillance by existing neoplasms at the time of initiation but insufficiently developed to detect with the currently available methods.
The vigilant post-marketing surveillance of medicinal products is vital, due to the circumstances of clinical trials, which make it possible to find that in current practice medication is also used in categories of patients explicitly excluded in clinical trials and, therefore, data on safety are relatively incomplete, if any at all. Meta-analyzes support a number of these disadvantages of clinical trials, primarily the limited number of patients. However, the duration of individual exposure to active molecules does not change, although data are reported in the patient-years of statistical form type of exposure…
A meta-analysis of 9 clinical trials shows a 3-fold higher risk (OR 3.3 with 95% CI) to develop malignancy in anti-\u03b1-TNF-treated patients compared to the control, the risk being proportional to the dose administered. NB, the rate of cancer in the study mentioned in the control arm was abnormally low…
To illustrate this reality we present a clinical case illustrative for the risks to both patients and physicians, despite the good faith of both.<\/p>\n
Scurt CV<\/span><\/p>\nMedic primar dermatovenerologie
Doctor \u00een \u015ftiin\u0163e medicale – Studiul microcircula\u0163iei sanguine \u00een patologia cutanat\u0103.
Coordonator activitate de cercetare, studii clinice la Spitalul Universitar de Urgen\u0163\u0103 Militar Central \u201eDr. Carol Davila\u201d, Bucure\u015fti.
Editor executiv, Romanian Journal of Military Medicine, revist\u0103 editat\u0103 de Asocia\u0163ia Medicilor \u015fi Farmaci\u015ftilor Militari din Rom\u00e2nia, Universitatea de Medicin\u0103 \u015fi Farmacie “Carol Davila” Bucure\u0219ti.
Delegat Ministerul Ap\u0103r\u0103rii Na\u0163ionale \u00een Consiliul Na\u0163ional al Colegiului Medicilor din Rom\u00e2nia.
Activitate clinic\u0103 \u015fi de cercetare \u00een cadrul departamentului de Dermatologie al Spitalului Universitar de Urgen\u0163\u0103 Militar Central \u201dDr. Carol Davila\u201d, Bucure\u015fti.
Competen\u0163\u0103 \u00een evaluarea microcircula\u0163iei.
Competen\u0163\u0103 \u00een electrochirurgie \u015fi laser chirurgie \u00een dermatologie.
Formator de formatori \u00een dermatocosmetologie.<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”3.19.4″ background_color=”rgba(117,194,33,0.23)” background_image=”https:\/\/pdi.ro\/2019\/wp-content\/uploads\/2019\/01\/back_justflowers_overlay1.png” background_blend=”luminosity” custom_padding=”54px|0px|0|0px|false|false” top_divider_style=”waves2″ top_divider_color=”#ffffff” top_divider_height=”155px” bottom_divider_style=”waves2″ bottom_divider_color=”#75c221″ bottom_divider_flip=”vertical”][et_pb_row custom_padding=”61px|0px|69px|0px|false|false” _builder_version=”3.18.9″][et_pb_column type=”3_5″ _builder_version=”3.18.9″][et_pb_text _builder_version=”3.19.4″ text_font=”Kaushan Script||||||||” text_text_color=”#f0622a” text_font_size=”30px” header_font=”||||||||” background_layout=”dark”]<\/p>\n
Contacteaz\u0103 operatorul PDI 2019<\/p>\n
[\/et_pb_text][et_pb_contact_form email=”contact@pdi.ro\/2019″ submit_button_text=”Trimite mesajul” _builder_version=”3.19.4″ title_font=”||||||||”][et_pb_contact_field field_id=”Name” field_title=”Nume” _builder_version=”3.18.9″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][et_pb_contact_field field_id=”Email” field_title=”Adresa de e-mail” field_type=”email” _builder_version=”3.19.4″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][et_pb_contact_field field_id=”Message” field_title=”Mesajul dvs.” field_type=”text” fullwidth_field=”on” _builder_version=”3.18.9″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][\/et_pb_contact_form][\/et_pb_column][et_pb_column type=”2_5″ _builder_version=”3.18.9″][et_pb_text _builder_version=”3.19.4″ text_font=”Kaushan Script||||||||” text_text_color=”#f0622a” text_font_size=”30px” header_font=”||||||||” background_layout=”dark”]<\/p>\n
Operatorul PDI 2019<\/p>\n
[\/et_pb_text][et_pb_text _builder_version=”3.19.4″ text_font=”||||||||”]<\/span><\/p>\n<\/span><\/p>\n<\/span><\/p>\nAdresa: Str. A. Panu nr. 13, Iasi<\/span>
\nTel.: 0332.40.88.00-05<\/span>
\nE-mail: inscrieri@pdi.ro\/2019<\/a>
\n<\/span>Website:\u00a0<\/span>www.eventernet.ro<\/a>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"Dr.\u00a0Costache\u00a0Daniel Spitalul Universitar de Urgen\u0163\u0103 Militar Central “Dr. Carol Davila\u201dExist\u0103 o leg\u0103tur\u0103 \u00eentre terapia biologic\u0103 \u00een psoriazis \u0219i cancerul de organ? Autori: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache La baza terapiilor moderne se afl\u0103 doi piloni fundamentali, anume pe de o parte studiile clinice cu num\u0103r semnificativ de pacien\u0163i, \u015fi pe de […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"class_list":["post-4091","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/comments?post=4091"}],"version-history":[{"count":8,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091\/revisions"}],"predecessor-version":[{"id":4726,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091\/revisions\/4726"}],"wp:attachment":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/media?parent=4091"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
Dr.\u00a0Costache\u00a0Daniel<\/strong><\/span>
Spitalul Universitar de Urgen\u0163\u0103 Militar Central “Dr. Carol Davila\u201d<\/strong><\/span><\/h4>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”3.19.14″][et_pb_column type=”4_4″ _builder_version=”3.19.14″][et_pb_text _builder_version=”3.19.18″]<\/p>\n
Exist\u0103 o leg\u0103tur\u0103 \u00eentre terapia biologic\u0103 \u00een psoriazis \u0219i cancerul de organ?<\/span>
Autori: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache<\/span><\/p>\nLa baza terapiilor moderne se afl\u0103 doi piloni fundamentali, anume pe de o parte studiile clinice cu num\u0103r semnificativ de pacien\u0163i, \u015fi pe de alt\u0103 parte experien\u0163a clinic\u0103 acumulat\u0103 pe milioane de pacien\u0163i.
Prin \u00eensumarea acestor doi factori fundamentali se ob\u021bin rezultate complexe, nu \u00eentotdeauna congruente, dar care permit s\u0103 analiz\u0103m \u00een termeni c\u00e2t se poate de obiectivi at\u00e2t eficacitatea tratamentului, c\u00e2t \u015fi siguran\u0163a produselor farmacologice utilizate \u015fi, nu \u00een ultimul r\u00e2nd, profilul pacien\u0163ilor candida\u0163i pentru tratament.
Exist\u0103 frecvent asocieri sau favoriz\u0103ri patologice \u00een afec\u0163iuni precum psoriazis vulgar sau boala Crohn. Ast\u0103zi, nimeni nu se mai mir\u0103 atunci c\u00e2nd constat\u0103 la un pacient psoriatic coexisten\u0163a sindromului metabolic, a afec\u0163iunilor intestinale inflamatorii, depresiei sau afec\u0163iunilor cardiace inflamatorii, punctul comun al acestora fiind inflama\u0163ia necontrolat\u0103 sistemic\u0103 declan\u015fat\u0103 de o cauz\u0103 necunoscut\u0103.
\u015etiut\u0103 fiind implicarea sistemului inflamator \u00een controlul multiplic\u0103rii celulare \u00een organism, discu\u0163ia despre corela\u0163iile \u00eentre sindromul inflamator cronic sistemic \u015fi tumorile hematologice sau de organ este absolut fireasc\u0103. Exist\u0103 numeroase dovezi referitoare la rolul \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale, fiind \u00een prezent definite cel pu\u0163in \u015fase aspecte caracteristice care ofer\u0103 celulelor avantaje de supravie\u0163uire in vivo. Aceste aspecte sunt: promovarea unor semnale autocrine de cre\u015ftere celular\u0103, instalarea insensibilit\u0103\u0163ii la semnalele anti-cre\u015ftere, favorizarea angiogenezei, evitarea c\u0103ilor apoptozei, favorizarea mecanismelor de invazivitate tisular\u0103 \u015fi de metastazare, replicarea celular\u0103 nerestric\u0163ionat\u0103.
Numeroase studii dovedesc implicarea \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale.
Tabelul 1: \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale
– produc\u0163ie de NO (alter\u0103ri ale ADN, promovare tumoral\u0103 cGMP mediat\u0103)
– cre\u015ftere autocrin\u0103 \u015fi factor de supravie\u0163uire pentru celule maligne
– activarea E6\/E7 ARNm \u00een celulele infectate cu HPV
– activarea Src kinazei
– remodelare tisular\u0103 prin matrix metaloproteinaze
– controlul infiltr\u0103rii leucocitare prin modulare citokinic\u0103
– inhibarea E-caderinei, cre\u015ftere nucleolar\u0103 de b catenin\u0103
– cre\u015fterea motilit\u0103\u0163ii (invazivit\u0103\u0163ii) tumorale
– tranzi\u0163ie epitelial-mezenchimal\u0103
– induc\u0163ie de factori angiogenici
– pierderea r\u0103spunsului la androgeni
– rezisten\u0163\u0103 la medica\u0163ie citotoxic\u0103
Datorit\u0103 acestor efecte deosebit de complexe \u015fi de complementare \u00een acela\u015fi timp, care arat\u0103 dincolo de orice comentarii c\u0103 organismul este posesorul unei balan\u0163e extrem de bine reglat\u0103 \u00een privin\u0163a mecanismelor sale inflamatorii de ap\u0103rare antitumoral\u0103, un tratament imunomodulator care s\u0103 influen\u0163eze titrurile circulante \u015fi tisulare de TNF poate pe drept cuv\u00e2nt s\u0103 ridice semne de \u00eentrebare \u015fi \u00eengrijor\u0103ri.
Tabelul 2: \u03b1-TNF \u00een combaterea neoplaziei
– injectarea de TNF intratumoral \u2013 oprirea fluxului sanguin, hemoragii intratumorale, necroz\u0103 vascular\u0103
– colonizare tumoral\u0103 cu PMN
– inhibarea cre\u015fterii tumorale prin macrofage \u015fi celule NK (Blankenstein, 1991)
– distruc\u0163ie \u015fi rejec\u0163ie tumoral\u0103 NK \u015fi LAK induse (Baxevanis, 2000)
– imunitate antitumoral\u0103 \u015fi eliminarea CTL indus\u0103 a tumorilor
– favorizarea apoptozei citocrom c mitocondrial indus\u0103
– apoptoz\u0103 c-myc dependent\u0103
– inhibarea activ\u0103rii NF-kB
Studiile clinice efectuate, metaanalizele, datele din registrele interna\u0163ionale, dar \u015fi, nu \u00een ultimul r\u00e2nd, experien\u0163a clinic\u0103 a speciali\u015ftilor sunt instrumentele puternice pe care le avem la \u00eendem\u00e2n\u0103 atunci c\u00e2nd facem afirma\u0163ia c\u0103 p\u00e2n\u0103 la acest moment nu exist\u0103 niciun fel de date care s\u0103 arate c\u0103 terapiile anti \u03b1-TNF ar fi incriminate \u00een induc\u0163ia neoplaziilor, fie ele de organ sau hematologice. Preocup\u0103rile ini\u0163iale care legau terapia biologic\u0103 de dezvoltarea limfoamelor par, \u00een lumina informa\u0163iilor actuale, desuete.
Cu toate acestea, ar fi o dovad\u0103 de iresponsabilitate s\u0103 nu admitem c\u0103 terapia biologic\u0103, ca toate formulele terapeutice cu un grad de imunosupresie de altfel, nu ar putea s\u0103 favorizeze dezvoltarea unei neoplazii, fie preexistent\u0103 fie de novo. Prin tulburarea balan\u0163ei mai sus prezentat\u0103 sumar, terapiile biologice anti \u03b1-TNF pot ajuta \u00eentr-o m\u0103sur\u0103 impredictibil\u0103 evitarea supravegherii imune de c\u0103tre neoplaziile existente la momentul ini\u0163ierii tratamentului, dar insuficient dezvoltate pentru a fi depistate cu metodele disponibile \u00een prezent.
Supravegherea vigilent\u0103 post marketing a produselor medicamentoase este vital\u0103, datorit\u0103 circumstan\u0163elor studiilor clinice, care fac s\u0103 se ajung\u0103 la situa\u0163ia c\u0103 \u00een practica curent\u0103 se utilizeaz\u0103 medicamente inclusiv la categorii de pacien\u0163i care au fost exclu\u015fi explicit \u00een studiile clinice \u015fi fa\u0163\u0103 de care \u00een consecin\u0163\u0103 datele privind siguran\u0163a sunt relativ incomplete, dac\u0103 exist\u0103 c\u00e2t de c\u00e2t. Metaanalizele suplinesc o serie din aceste dezavantaje ale studiilor clinice, \u00een primul r\u00e2nd num\u0103rul limitat de pacien\u0163i. Durata de expunere individual\u0103 la moleculele active \u00eens\u0103 nu se modific\u0103, de\u015fi datele sunt comunicate sub form\u0103 statistic\u0103 de tip pacient-ani de expunere…
O metaanaliz\u0103 pe 9 studii clinice arat\u0103 un risc de 3 ori mai mare (OR 3,3 cu CI 95%) de a dezvolta o malignitate la pacien\u0163ii trata\u0163i cu anti \u03b1-TNF fa\u0163\u0103 de martor, riscul fiind propor\u0163ional cu doza administrat\u0103. Nota bene, \u00een studiul men\u0163ionat rata de neoplazii \u00een bra\u0163ul de control a fost anormal de sc\u0103zut\u0103…
Pentru a ilustra aceast\u0103 realitate prezent\u0103m un caz clinic, ilustrativ pentru riscurile la care sunt expu\u015fi \u00een acela\u015fi timp \u015fi pacien\u0163ii dar \u015fi medicii, \u00een ciuda bunei credin\u0163e a ambilor.<\/p>\n
Is there a link between biological therapy in psoriasis and organ cancer?<\/span>
Authors: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache<\/span><\/p>\nAt the basis of modern therapies there are two fundamental pillars, namely the clinical trials with a significant number of patients on one hand and the clinical experience accumulated on millions of patients on the other hand.
By summing up these two fundamental factors we obtain complex results, not always congruent, but which allow us to analyze in objective terms both the efficacy of the treatment and the safety of the pharmacological products used and, last but not least, the profile of the candidates for treatment.
There is often a bias association or pathological conditions such as vulgar psoriasis or Crohn’s disease. Today no one is surprised to find out to a psoriatic patient the coexistence of metabolic syndrome, inflammatory bowel disease, depression or inflammatory heart disease, their common point being the uncontrolled systemic inflammation triggered by an unknown cause.
Knowing the involvement of the inflammatory system in the control of cellular multiplication in the body, the discussion about the correlations between chronic systemic inflammatory syndrome and hematological or organ tumors is absolutely natural. There is ample evidence on the role of TNF-\u03b1 in regulating tumor promotion and propagation and at least six characteristic aspects are currently set offering advantages to cells for in vivo survival. These aspects are: promoting autocrine cell growth signals, installing insensitivity to anti-growth signals, favoring angiogenesis, avoiding apoptosis pathways, favoring tissue and metastasis invasiveness mechanisms, unrestricted cellular replication.
Numerous studies prove the involvement of TNF-\u03b1 in regulating tumor promotion and propagation.
Table 1: TNF-\u03b1 in the regulation of tumor promotion and propagation
– production of NO (DNA alterations, mediated cGMP tumor promotion)
– autocrine growth and survival factor for malignant cells
– activation of E6 \/ E7 mRNA in HPV-infected cells
– activation of Src kinase
– tissue remodeling by matrix metalloproteinases
– control of leukocyte infiltration by cytokine modulation
– inhibition of E-cadherin, nucleolar growth of b catenin
– increased tumor motility (invasiveness)
– epithelial-mesenchymal transition
– induction of angiogenic factors
– loss of androgen response
– resistance to cytotoxic medication
Because of these particularly complex and complementary effects at the same time which shows beyond any comments that the body has very well-balanced scales regarding its inflammatory mechanisms of antitumor defense, an immunomodulatory treatment to influence circulating and tissue titres of TNF can rightly raise questions and concerns.
Table 2: TNF-\u03b1 in counteracting neoplasia
– intratumoral TNF injection – blood flow stop, intratumoral haemorrhage, vascular necrosis
– PMN tumor colonization
– inhibition of tumor growth by macrophages and NK cells (Blankenstein, 1991)
– NK and LAK induced tumor destruction and rejection (Baxevanis, 2000)
– antitumor immunity and elimination of tumor-induced CTL
– favoring induced cytochrome c mitochondrial apoptosis
– c-myc dependent apoptosis
– inhibition of NF-\u03baB activation
Clinical trials, meta-analyzes, data from international registries and last but not least the clinical experience of specialists are the powerful tools we have at hand when we assert that there is no data to date that anti-\u03b1-TNF therapies would be incriminated in the induction of neoplasia whether organ or hematologic. The initial concerns that linked biological therapy to the development of lymphomas appear in the light of current information as obsolete.
However, it would be irresponsible not to admit that biological therapy, like all other immunosuppressed therapeutic formulas, could not favor the development of a pre-existing or de novo neoplasm. By analyzing the above-mentioned balance disorder, anti-\u03b1-TNF biological therapies may, to an unpredictable extent, help to avoid immune surveillance by existing neoplasms at the time of initiation but insufficiently developed to detect with the currently available methods.
The vigilant post-marketing surveillance of medicinal products is vital, due to the circumstances of clinical trials, which make it possible to find that in current practice medication is also used in categories of patients explicitly excluded in clinical trials and, therefore, data on safety are relatively incomplete, if any at all. Meta-analyzes support a number of these disadvantages of clinical trials, primarily the limited number of patients. However, the duration of individual exposure to active molecules does not change, although data are reported in the patient-years of statistical form type of exposure…
A meta-analysis of 9 clinical trials shows a 3-fold higher risk (OR 3.3 with 95% CI) to develop malignancy in anti-\u03b1-TNF-treated patients compared to the control, the risk being proportional to the dose administered. NB, the rate of cancer in the study mentioned in the control arm was abnormally low…
To illustrate this reality we present a clinical case illustrative for the risks to both patients and physicians, despite the good faith of both.<\/p>\n
Scurt CV<\/span><\/p>\nMedic primar dermatovenerologie
Doctor \u00een \u015ftiin\u0163e medicale – Studiul microcircula\u0163iei sanguine \u00een patologia cutanat\u0103.
Coordonator activitate de cercetare, studii clinice la Spitalul Universitar de Urgen\u0163\u0103 Militar Central \u201eDr. Carol Davila\u201d, Bucure\u015fti.
Editor executiv, Romanian Journal of Military Medicine, revist\u0103 editat\u0103 de Asocia\u0163ia Medicilor \u015fi Farmaci\u015ftilor Militari din Rom\u00e2nia, Universitatea de Medicin\u0103 \u015fi Farmacie “Carol Davila” Bucure\u0219ti.
Delegat Ministerul Ap\u0103r\u0103rii Na\u0163ionale \u00een Consiliul Na\u0163ional al Colegiului Medicilor din Rom\u00e2nia.
Activitate clinic\u0103 \u015fi de cercetare \u00een cadrul departamentului de Dermatologie al Spitalului Universitar de Urgen\u0163\u0103 Militar Central \u201dDr. Carol Davila\u201d, Bucure\u015fti.
Competen\u0163\u0103 \u00een evaluarea microcircula\u0163iei.
Competen\u0163\u0103 \u00een electrochirurgie \u015fi laser chirurgie \u00een dermatologie.
Formator de formatori \u00een dermatocosmetologie.<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”3.19.4″ background_color=”rgba(117,194,33,0.23)” background_image=”https:\/\/pdi.ro\/2019\/wp-content\/uploads\/2019\/01\/back_justflowers_overlay1.png” background_blend=”luminosity” custom_padding=”54px|0px|0|0px|false|false” top_divider_style=”waves2″ top_divider_color=”#ffffff” top_divider_height=”155px” bottom_divider_style=”waves2″ bottom_divider_color=”#75c221″ bottom_divider_flip=”vertical”][et_pb_row custom_padding=”61px|0px|69px|0px|false|false” _builder_version=”3.18.9″][et_pb_column type=”3_5″ _builder_version=”3.18.9″][et_pb_text _builder_version=”3.19.4″ text_font=”Kaushan Script||||||||” text_text_color=”#f0622a” text_font_size=”30px” header_font=”||||||||” background_layout=”dark”]<\/p>\n
Contacteaz\u0103 operatorul PDI 2019<\/p>\n
[\/et_pb_text][et_pb_contact_form email=”contact@pdi.ro\/2019″ submit_button_text=”Trimite mesajul” _builder_version=”3.19.4″ title_font=”||||||||”][et_pb_contact_field field_id=”Name” field_title=”Nume” _builder_version=”3.18.9″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][et_pb_contact_field field_id=”Email” field_title=”Adresa de e-mail” field_type=”email” _builder_version=”3.19.4″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][et_pb_contact_field field_id=”Message” field_title=”Mesajul dvs.” field_type=”text” fullwidth_field=”on” _builder_version=”3.18.9″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][\/et_pb_contact_form][\/et_pb_column][et_pb_column type=”2_5″ _builder_version=”3.18.9″][et_pb_text _builder_version=”3.19.4″ text_font=”Kaushan Script||||||||” text_text_color=”#f0622a” text_font_size=”30px” header_font=”||||||||” background_layout=”dark”]<\/p>\n
Operatorul PDI 2019<\/p>\n
[\/et_pb_text][et_pb_text _builder_version=”3.19.4″ text_font=”||||||||”]<\/span><\/p>\n<\/span><\/p>\n<\/span><\/p>\nAdresa: Str. A. Panu nr. 13, Iasi<\/span>
\nTel.: 0332.40.88.00-05<\/span>
\nE-mail: inscrieri@pdi.ro\/2019<\/a>
\n<\/span>Website:\u00a0<\/span>www.eventernet.ro<\/a>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"Dr.\u00a0Costache\u00a0Daniel Spitalul Universitar de Urgen\u0163\u0103 Militar Central “Dr. Carol Davila\u201dExist\u0103 o leg\u0103tur\u0103 \u00eentre terapia biologic\u0103 \u00een psoriazis \u0219i cancerul de organ? Autori: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache La baza terapiilor moderne se afl\u0103 doi piloni fundamentali, anume pe de o parte studiile clinice cu num\u0103r semnificativ de pacien\u0163i, \u015fi pe de […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"class_list":["post-4091","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/comments?post=4091"}],"version-history":[{"count":8,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091\/revisions"}],"predecessor-version":[{"id":4726,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091\/revisions\/4726"}],"wp:attachment":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/media?parent=4091"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
Autori: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache<\/span><\/p>\n
La baza terapiilor moderne se afl\u0103 doi piloni fundamentali, anume pe de o parte studiile clinice cu num\u0103r semnificativ de pacien\u0163i, \u015fi pe de alt\u0103 parte experien\u0163a clinic\u0103 acumulat\u0103 pe milioane de pacien\u0163i.
Prin \u00eensumarea acestor doi factori fundamentali se ob\u021bin rezultate complexe, nu \u00eentotdeauna congruente, dar care permit s\u0103 analiz\u0103m \u00een termeni c\u00e2t se poate de obiectivi at\u00e2t eficacitatea tratamentului, c\u00e2t \u015fi siguran\u0163a produselor farmacologice utilizate \u015fi, nu \u00een ultimul r\u00e2nd, profilul pacien\u0163ilor candida\u0163i pentru tratament.
Exist\u0103 frecvent asocieri sau favoriz\u0103ri patologice \u00een afec\u0163iuni precum psoriazis vulgar sau boala Crohn. Ast\u0103zi, nimeni nu se mai mir\u0103 atunci c\u00e2nd constat\u0103 la un pacient psoriatic coexisten\u0163a sindromului metabolic, a afec\u0163iunilor intestinale inflamatorii, depresiei sau afec\u0163iunilor cardiace inflamatorii, punctul comun al acestora fiind inflama\u0163ia necontrolat\u0103 sistemic\u0103 declan\u015fat\u0103 de o cauz\u0103 necunoscut\u0103.
\u015etiut\u0103 fiind implicarea sistemului inflamator \u00een controlul multiplic\u0103rii celulare \u00een organism, discu\u0163ia despre corela\u0163iile \u00eentre sindromul inflamator cronic sistemic \u015fi tumorile hematologice sau de organ este absolut fireasc\u0103. Exist\u0103 numeroase dovezi referitoare la rolul \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale, fiind \u00een prezent definite cel pu\u0163in \u015fase aspecte caracteristice care ofer\u0103 celulelor avantaje de supravie\u0163uire in vivo. Aceste aspecte sunt: promovarea unor semnale autocrine de cre\u015ftere celular\u0103, instalarea insensibilit\u0103\u0163ii la semnalele anti-cre\u015ftere, favorizarea angiogenezei, evitarea c\u0103ilor apoptozei, favorizarea mecanismelor de invazivitate tisular\u0103 \u015fi de metastazare, replicarea celular\u0103 nerestric\u0163ionat\u0103.
Numeroase studii dovedesc implicarea \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale.
Tabelul 1: \u03b1-TNF \u00een reglarea promov\u0103rii \u015fi propag\u0103rii tumorale
– produc\u0163ie de NO (alter\u0103ri ale ADN, promovare tumoral\u0103 cGMP mediat\u0103)
– cre\u015ftere autocrin\u0103 \u015fi factor de supravie\u0163uire pentru celule maligne
– activarea E6\/E7 ARNm \u00een celulele infectate cu HPV
– activarea Src kinazei
– remodelare tisular\u0103 prin matrix metaloproteinaze
– controlul infiltr\u0103rii leucocitare prin modulare citokinic\u0103
– inhibarea E-caderinei, cre\u015ftere nucleolar\u0103 de b catenin\u0103
– cre\u015fterea motilit\u0103\u0163ii (invazivit\u0103\u0163ii) tumorale
– tranzi\u0163ie epitelial-mezenchimal\u0103
– induc\u0163ie de factori angiogenici
– pierderea r\u0103spunsului la androgeni
– rezisten\u0163\u0103 la medica\u0163ie citotoxic\u0103
Datorit\u0103 acestor efecte deosebit de complexe \u015fi de complementare \u00een acela\u015fi timp, care arat\u0103 dincolo de orice comentarii c\u0103 organismul este posesorul unei balan\u0163e extrem de bine reglat\u0103 \u00een privin\u0163a mecanismelor sale inflamatorii de ap\u0103rare antitumoral\u0103, un tratament imunomodulator care s\u0103 influen\u0163eze titrurile circulante \u015fi tisulare de TNF poate pe drept cuv\u00e2nt s\u0103 ridice semne de \u00eentrebare \u015fi \u00eengrijor\u0103ri.
Tabelul 2: \u03b1-TNF \u00een combaterea neoplaziei
– injectarea de TNF intratumoral \u2013 oprirea fluxului sanguin, hemoragii intratumorale, necroz\u0103 vascular\u0103
– colonizare tumoral\u0103 cu PMN
– inhibarea cre\u015fterii tumorale prin macrofage \u015fi celule NK (Blankenstein, 1991)
– distruc\u0163ie \u015fi rejec\u0163ie tumoral\u0103 NK \u015fi LAK induse (Baxevanis, 2000)
– imunitate antitumoral\u0103 \u015fi eliminarea CTL indus\u0103 a tumorilor
– favorizarea apoptozei citocrom c mitocondrial indus\u0103
– apoptoz\u0103 c-myc dependent\u0103
– inhibarea activ\u0103rii NF-kB
Studiile clinice efectuate, metaanalizele, datele din registrele interna\u0163ionale, dar \u015fi, nu \u00een ultimul r\u00e2nd, experien\u0163a clinic\u0103 a speciali\u015ftilor sunt instrumentele puternice pe care le avem la \u00eendem\u00e2n\u0103 atunci c\u00e2nd facem afirma\u0163ia c\u0103 p\u00e2n\u0103 la acest moment nu exist\u0103 niciun fel de date care s\u0103 arate c\u0103 terapiile anti \u03b1-TNF ar fi incriminate \u00een induc\u0163ia neoplaziilor, fie ele de organ sau hematologice. Preocup\u0103rile ini\u0163iale care legau terapia biologic\u0103 de dezvoltarea limfoamelor par, \u00een lumina informa\u0163iilor actuale, desuete.
Cu toate acestea, ar fi o dovad\u0103 de iresponsabilitate s\u0103 nu admitem c\u0103 terapia biologic\u0103, ca toate formulele terapeutice cu un grad de imunosupresie de altfel, nu ar putea s\u0103 favorizeze dezvoltarea unei neoplazii, fie preexistent\u0103 fie de novo. Prin tulburarea balan\u0163ei mai sus prezentat\u0103 sumar, terapiile biologice anti \u03b1-TNF pot ajuta \u00eentr-o m\u0103sur\u0103 impredictibil\u0103 evitarea supravegherii imune de c\u0103tre neoplaziile existente la momentul ini\u0163ierii tratamentului, dar insuficient dezvoltate pentru a fi depistate cu metodele disponibile \u00een prezent.
Supravegherea vigilent\u0103 post marketing a produselor medicamentoase este vital\u0103, datorit\u0103 circumstan\u0163elor studiilor clinice, care fac s\u0103 se ajung\u0103 la situa\u0163ia c\u0103 \u00een practica curent\u0103 se utilizeaz\u0103 medicamente inclusiv la categorii de pacien\u0163i care au fost exclu\u015fi explicit \u00een studiile clinice \u015fi fa\u0163\u0103 de care \u00een consecin\u0163\u0103 datele privind siguran\u0163a sunt relativ incomplete, dac\u0103 exist\u0103 c\u00e2t de c\u00e2t. Metaanalizele suplinesc o serie din aceste dezavantaje ale studiilor clinice, \u00een primul r\u00e2nd num\u0103rul limitat de pacien\u0163i. Durata de expunere individual\u0103 la moleculele active \u00eens\u0103 nu se modific\u0103, de\u015fi datele sunt comunicate sub form\u0103 statistic\u0103 de tip pacient-ani de expunere…
O metaanaliz\u0103 pe 9 studii clinice arat\u0103 un risc de 3 ori mai mare (OR 3,3 cu CI 95%) de a dezvolta o malignitate la pacien\u0163ii trata\u0163i cu anti \u03b1-TNF fa\u0163\u0103 de martor, riscul fiind propor\u0163ional cu doza administrat\u0103. Nota bene, \u00een studiul men\u0163ionat rata de neoplazii \u00een bra\u0163ul de control a fost anormal de sc\u0103zut\u0103…
Pentru a ilustra aceast\u0103 realitate prezent\u0103m un caz clinic, ilustrativ pentru riscurile la care sunt expu\u015fi \u00een acela\u015fi timp \u015fi pacien\u0163ii dar \u015fi medicii, \u00een ciuda bunei credin\u0163e a ambilor.<\/p>\n
Is there a link between biological therapy in psoriasis and organ cancer?<\/span> At the basis of modern therapies there are two fundamental pillars, namely the clinical trials with a significant number of patients on one hand and the clinical experience accumulated on millions of patients on the other hand. Scurt CV<\/span><\/p>\n Medic primar dermatovenerologie [\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”3.19.4″ background_color=”rgba(117,194,33,0.23)” background_image=”https:\/\/pdi.ro\/2019\/wp-content\/uploads\/2019\/01\/back_justflowers_overlay1.png” background_blend=”luminosity” custom_padding=”54px|0px|0|0px|false|false” top_divider_style=”waves2″ top_divider_color=”#ffffff” top_divider_height=”155px” bottom_divider_style=”waves2″ bottom_divider_color=”#75c221″ bottom_divider_flip=”vertical”][et_pb_row custom_padding=”61px|0px|69px|0px|false|false” _builder_version=”3.18.9″][et_pb_column type=”3_5″ _builder_version=”3.18.9″][et_pb_text _builder_version=”3.19.4″ text_font=”Kaushan Script||||||||” text_text_color=”#f0622a” text_font_size=”30px” header_font=”||||||||” background_layout=”dark”]<\/p>\n Contacteaz\u0103 operatorul PDI 2019<\/p>\n [\/et_pb_text][et_pb_contact_form email=”contact@pdi.ro\/2019″ submit_button_text=”Trimite mesajul” _builder_version=”3.19.4″ title_font=”||||||||”][et_pb_contact_field field_id=”Name” field_title=”Nume” _builder_version=”3.18.9″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][et_pb_contact_field field_id=”Email” field_title=”Adresa de e-mail” field_type=”email” _builder_version=”3.19.4″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][et_pb_contact_field field_id=”Message” field_title=”Mesajul dvs.” field_type=”text” fullwidth_field=”on” _builder_version=”3.18.9″ border_radii=”on||||” button_text_size__hover_enabled=”off” button_one_text_size__hover_enabled=”off” button_two_text_size__hover_enabled=”off” button_text_color__hover_enabled=”off” button_one_text_color__hover_enabled=”off” button_two_text_color__hover_enabled=”off” button_border_width__hover_enabled=”off” button_one_border_width__hover_enabled=”off” button_two_border_width__hover_enabled=”off” button_border_color__hover_enabled=”off” button_one_border_color__hover_enabled=”off” button_two_border_color__hover_enabled=”off” button_border_radius__hover_enabled=”off” button_one_border_radius__hover_enabled=”off” button_two_border_radius__hover_enabled=”off” button_letter_spacing__hover_enabled=”off” button_one_letter_spacing__hover_enabled=”off” button_two_letter_spacing__hover_enabled=”off” button_bg_color__hover_enabled=”off” button_one_bg_color__hover_enabled=”off” button_two_bg_color__hover_enabled=”off”][\/et_pb_contact_field][\/et_pb_contact_form][\/et_pb_column][et_pb_column type=”2_5″ _builder_version=”3.18.9″][et_pb_text _builder_version=”3.19.4″ text_font=”Kaushan Script||||||||” text_text_color=”#f0622a” text_font_size=”30px” header_font=”||||||||” background_layout=”dark”]<\/p>\n Operatorul PDI 2019<\/p>\n [\/et_pb_text][et_pb_text _builder_version=”3.19.4″ text_font=”||||||||”] <\/span><\/p>\n <\/span><\/p>\n Adresa: Str. A. Panu nr. 13, Iasi<\/span> Dr.\u00a0Costache\u00a0Daniel Spitalul Universitar de Urgen\u0163\u0103 Militar Central “Dr. Carol Davila\u201dExist\u0103 o leg\u0103tur\u0103 \u00eentre terapia biologic\u0103 \u00een psoriazis \u0219i cancerul de organ? Autori: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache La baza terapiilor moderne se afl\u0103 doi piloni fundamentali, anume pe de o parte studiile clinice cu num\u0103r semnificativ de pacien\u0163i, \u015fi pe de […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"class_list":["post-4091","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/comments?post=4091"}],"version-history":[{"count":8,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091\/revisions"}],"predecessor-version":[{"id":4726,"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/pages\/4091\/revisions\/4726"}],"wp:attachment":[{"href":"https:\/\/pdi.ro\/2019\/wp-json\/wp\/v2\/media?parent=4091"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
Authors: D. O. Costache, Alexandra I. Lulache, Raluca S. Costache<\/span><\/p>\n
By summing up these two fundamental factors we obtain complex results, not always congruent, but which allow us to analyze in objective terms both the efficacy of the treatment and the safety of the pharmacological products used and, last but not least, the profile of the candidates for treatment.
There is often a bias association or pathological conditions such as vulgar psoriasis or Crohn’s disease. Today no one is surprised to find out to a psoriatic patient the coexistence of metabolic syndrome, inflammatory bowel disease, depression or inflammatory heart disease, their common point being the uncontrolled systemic inflammation triggered by an unknown cause.
Knowing the involvement of the inflammatory system in the control of cellular multiplication in the body, the discussion about the correlations between chronic systemic inflammatory syndrome and hematological or organ tumors is absolutely natural. There is ample evidence on the role of TNF-\u03b1 in regulating tumor promotion and propagation and at least six characteristic aspects are currently set offering advantages to cells for in vivo survival. These aspects are: promoting autocrine cell growth signals, installing insensitivity to anti-growth signals, favoring angiogenesis, avoiding apoptosis pathways, favoring tissue and metastasis invasiveness mechanisms, unrestricted cellular replication.
Numerous studies prove the involvement of TNF-\u03b1 in regulating tumor promotion and propagation.
Table 1: TNF-\u03b1 in the regulation of tumor promotion and propagation
– production of NO (DNA alterations, mediated cGMP tumor promotion)
– autocrine growth and survival factor for malignant cells
– activation of E6 \/ E7 mRNA in HPV-infected cells
– activation of Src kinase
– tissue remodeling by matrix metalloproteinases
– control of leukocyte infiltration by cytokine modulation
– inhibition of E-cadherin, nucleolar growth of b catenin
– increased tumor motility (invasiveness)
– epithelial-mesenchymal transition
– induction of angiogenic factors
– loss of androgen response
– resistance to cytotoxic medication
Because of these particularly complex and complementary effects at the same time which shows beyond any comments that the body has very well-balanced scales regarding its inflammatory mechanisms of antitumor defense, an immunomodulatory treatment to influence circulating and tissue titres of TNF can rightly raise questions and concerns.
Table 2: TNF-\u03b1 in counteracting neoplasia
– intratumoral TNF injection – blood flow stop, intratumoral haemorrhage, vascular necrosis
– PMN tumor colonization
– inhibition of tumor growth by macrophages and NK cells (Blankenstein, 1991)
– NK and LAK induced tumor destruction and rejection (Baxevanis, 2000)
– antitumor immunity and elimination of tumor-induced CTL
– favoring induced cytochrome c mitochondrial apoptosis
– c-myc dependent apoptosis
– inhibition of NF-\u03baB activation
Clinical trials, meta-analyzes, data from international registries and last but not least the clinical experience of specialists are the powerful tools we have at hand when we assert that there is no data to date that anti-\u03b1-TNF therapies would be incriminated in the induction of neoplasia whether organ or hematologic. The initial concerns that linked biological therapy to the development of lymphomas appear in the light of current information as obsolete.
However, it would be irresponsible not to admit that biological therapy, like all other immunosuppressed therapeutic formulas, could not favor the development of a pre-existing or de novo neoplasm. By analyzing the above-mentioned balance disorder, anti-\u03b1-TNF biological therapies may, to an unpredictable extent, help to avoid immune surveillance by existing neoplasms at the time of initiation but insufficiently developed to detect with the currently available methods.
The vigilant post-marketing surveillance of medicinal products is vital, due to the circumstances of clinical trials, which make it possible to find that in current practice medication is also used in categories of patients explicitly excluded in clinical trials and, therefore, data on safety are relatively incomplete, if any at all. Meta-analyzes support a number of these disadvantages of clinical trials, primarily the limited number of patients. However, the duration of individual exposure to active molecules does not change, although data are reported in the patient-years of statistical form type of exposure…
A meta-analysis of 9 clinical trials shows a 3-fold higher risk (OR 3.3 with 95% CI) to develop malignancy in anti-\u03b1-TNF-treated patients compared to the control, the risk being proportional to the dose administered. NB, the rate of cancer in the study mentioned in the control arm was abnormally low…
To illustrate this reality we present a clinical case illustrative for the risks to both patients and physicians, despite the good faith of both.<\/p>\n
Doctor \u00een \u015ftiin\u0163e medicale – Studiul microcircula\u0163iei sanguine \u00een patologia cutanat\u0103.
Coordonator activitate de cercetare, studii clinice la Spitalul Universitar de Urgen\u0163\u0103 Militar Central \u201eDr. Carol Davila\u201d, Bucure\u015fti.
Editor executiv, Romanian Journal of Military Medicine, revist\u0103 editat\u0103 de Asocia\u0163ia Medicilor \u015fi Farmaci\u015ftilor Militari din Rom\u00e2nia, Universitatea de Medicin\u0103 \u015fi Farmacie “Carol Davila” Bucure\u0219ti.
Delegat Ministerul Ap\u0103r\u0103rii Na\u0163ionale \u00een Consiliul Na\u0163ional al Colegiului Medicilor din Rom\u00e2nia.
Activitate clinic\u0103 \u015fi de cercetare \u00een cadrul departamentului de Dermatologie al Spitalului Universitar de Urgen\u0163\u0103 Militar Central \u201dDr. Carol Davila\u201d, Bucure\u015fti.
Competen\u0163\u0103 \u00een evaluarea microcircula\u0163iei.
Competen\u0163\u0103 \u00een electrochirurgie \u015fi laser chirurgie \u00een dermatologie.
Formator de formatori \u00een dermatocosmetologie.<\/span><\/p>\n<\/span><\/p>\n
\nTel.: 0332.40.88.00-05<\/span>
\nE-mail: inscrieri@pdi.ro\/2019<\/a>
\n<\/span>Website:\u00a0<\/span>www.eventernet.ro<\/a>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"