سرطان البنكرياس هو مرض ذو معدل وفيات مرتفع، ولا يزال التشخيص المبكر لسرطان البنكرياس يمثل تحديًا. يظل معدل البقاء النسبي لمدة 5 سنوات أقل من 8%، والاستراتيجيات العلاجية غير فعالة في زيادة معدلات بقاء المريض على قيد الحياة. في خلايا سرطان البنكرياس، ارتبطت مقاومة العلاج بالتغيرات الجينية التي تؤدي إلى ظهور مسارات خلوية شاذة؛ ولذلك، هناك ما يبرر ايجاد استراتيجيات جديدة لعلاج هذا المرض. هنا، سعينا لاستكشاف مُنشط p53، APR-246، إما كدواء أحادي أو مدمج مع دوكسوروبيسين في خط خلايا AsPC-1 ذات بروتين p53 المتحول (p53-mut). تمت دراسة السمية الخلوية لـدوائي APR-246 ودوكوروبيسين اما منفردة أو مجتمعة في خط خلايا AsPC-1 مع اختبار MTT. تم حساب مؤشر معامل قياس التأزر (Combination Index) بناءً على نهج Chou و Talalay باستخدام برنامج CalcuSyn. تم تقييم موت الخلايا المبرمج بعد تصبيغها باستخداممادة الاكريدين اورنج/ايثيديوم برومايد (AO/EB). تم فحص التغيرات المورفولوجية تحت المجهر المقلوب بقوة تكبير 200 مرة تم قياس كمية التعبير الجيني باستخدام فحص النسخ العكسي الكمي PCR . أظهر APR-246 وحده تأثيرات متواضعة مضادة للتكاثر، في حين أظهر دوكسوروبيسين مع APR-246 تأثيرات تآزرية مرتبطة بالتغير المورفولوجي؛ لم يلاحظ أزدياد في نسبة موت الخلايا المبرمج في الخلايا المعاملة بكلا العقارين و هذا ما اكدته مستويات جين ال NOXA. في الختام، APR-246، سواء كان العلاج وحيدًا أو مقترنًا بـدوكسوروبيسين، كان يعيق تكاثر خلايا AsPC-1 ذات p53-mut، وهناك ما يبرر إجراء المزيد من الأبحاث في المختبر وفي الجسم الحي.
Pancreatic adenocarcinoma is one of the major causes of cancer death in the world. Alterations in p53 tumor suppressor gene
Carnosol, a phenolic diterpene, is one of the effective anticancer agents naturally occurring in rosemary, sage, parsley, and oregano. The chemoresistance problem increased with the routinely used chemotherapy. Therefore, the efforts to find a substitute with safe and low cost have become crucial worldwide. The current study attempts to inspect the anticancer molecular mechanisms of Carnosol on modulating up- and down- regulation of multiple genetic carcinogenesis pathways. The cytotoxicity of Carnosol on Hela cells was evaluated by MTS assay. Flow cytometry was used to assess apoptosis and cell cycle arrest. The apoptotic morphological changes were obvious by dual apoptosis assay. The differential gene expression after treatment wi
... Show MoreThe protective effect of benfotiamine against doxorubicin-induced cardiotoxicity was evaluated in rabbits. Pretreatment of rabbits with 70mg/kg benfotiamine orally 7 days before induction of cardiotoxicity with I.V 15mg/kg doxorubicin. injection resulted in significant reduction of the activities of lactate dehydrogenase and creatine phosphokinase enzyme in the serum compared to doxorubicin treated animals; benfotiamine also improves the histological changes produced by doxorubicin in the cardiac muscle compared to control. In conclusion, benfotiamine when used concomitantly with doxorubicin protects the myocardium against the cardiotoxicity induced by this cytotoxic drug.
Background: Doxorubicin is considered one of the most effective anticancer drugs, yet it is use is limited by its side effect mediated by the generation of reactive oxygen species. Omega-7, an antioxidant has shown to have a cardioprotective effect.
Aim of the study: evaluate a possible protective effect of omega-7 against doxorubicin-induced cardiotoxicity in male rats.
Methods: twenty-eight male rats were divided into 4 groups (7 for each group). Group 1 (Negative control): healthy animals received normal saline orally as the vehicle for eight successive days and were sacrificed on day 9. Group 2 (positive control): animals that r
... Show MoreThis study looked at how the synthetic chitosan-AgNPs-Doxorubicin-folic acid combination affected the A549 cell line in terms of cytotoxicity and anticancer activity. By reducing silver nitrate (AgNO3) and biodegradable chitosan, silver nanoparticles were biosynthesized. The produced conjugate was examined by using FT-IR spectroscopy, atomic force microscopy (AFM), and field emission scanning electron microscopy (FE-SEM). The cytotoxicity assay for the viability of A549 cells revealed that the combination of chitosan, AgNPs, doxorubicin, and folic acid decrease cell viability in a dose-determined by method over 48 hours, which direct to a dependent reduce in the activity of A549 cells. The mechanism analysis of the impacted living cells lea
... Show MoreCombination of natural poly-phenolic compounds with chemotherapeutic agents is recently being a novel strategy in cancer therapy researches owing to their potential antioxidant and anti-inflammatory properties that modulate several intracellular signaling pathways.
Resveratrol and Baicalein are well known poly-phenolic compounds that belong to stilbene and flavone subclasses, respectively.
This study aims to investigate the possible enhancement effect of resveratrol and Baicalein when combined with doxorubicin using a different combination ratio and applied on two cancer cell lines: HCT116 (colorectal cancer cells) and HepG2 (hepatocellular cancer cells). It also investigates the possibility of such natural compounds to p
... Show MoreDoxorubicin (DOX) is an efficient antineoplastic agent with a broad antitumor spectrum; however, doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application. Cafestol (Caf) is a naturally occurring diterpene in unfiltered coffee with unique antioxidant, antimutagenic, and anti-inflammatory activities by activating the Nrf2 pathway. The present study aimed to investigate the potential chemoprotective effect of cafestol on DOX-induced cardiotoxicity in rats. Wistar albino rats of both sexes were administered cafestol (5 mg/kg/day) for 14 consecutive days by oral gavage alone or with doxorubicin which was injected as a single dose (15 mg/kg intraperitoneally at day 14) to i
... Show MoreIn the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species in an iron-dependent manner.
Background: Radiation therapy has the ability to destroy healthy cells in addition to cancer cells in the area being treated. However, when radiation combines with doxorubicin, it becomes more effective on breast cancer treatment. Objective: This study aims to clarify the effect of X-ray from LINAC combined with amygdalin and doxorubicin on breast cancer treatment, and the possibility of using amygdalin with X-ray instead of doxorubicin for the breast cancer treatment. Method: Two cell lines were used in this study, the first one was MCF-7 cell line and second one was WRL- 68 normal cell line. These cells were preserved in liquid nitrogen, prepared, developed and tested in the (place). The effect of three x-ray doses combined with a
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