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3.
Cureus ; 14(1): e21121, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35165577

ABSTRACT

Inguinal hernia is a prevalent surgical condition worldwide. The hernia sac typically contains the omentum and small intestine. However, it has been reported that some other organs might be seen, including the ovary, fallopian tube, bladder, and colon. We report the case of a 23-year-old man who presented to our emergency department with the complaint of scrotal pain for the last six days. The pain was mainly in the right side. There was no history of preceding trauma, and the pain developed gradually. He described the pain as having a sharp nature and was constant. He reported having a low-grade fever that resolved with the use of over-the-counter analgesics. There was no change in the urine or bowel habits. No penile discharge was reported. On examination, the patient had a low-grade fever and tachycardia. The patient appeared in pain and was not cooperative to have a complete genitalia examination. However, there was a positive cough impulse in the right inguinal region. The laboratory findings suggested the presence of inflammatory or infectious processes with elevated leukocytes, C-reactive protein, and erythrocyte sedimentation rate. The patient was prepared for emergency laparotomy for reduction of the hernia and resection of the appendix. During exploration, the appendix was reduced from the hernia sac. The appendix appeared edematous, with marked erythema representing acute appendicitis. The appendix was resected and the hernia sac was closed. The presence of an appendix in the inguinal hernia sac is very rare. The preoperative diagnosis of Amyand hernia, the inguinal hernia containing the appendix, can be difficult based on the clinical presentation. Early diagnosis is crucial to avoid the potential complications of Amyand hernia, including perforation and abscess formation. Imaging studies can establish the diagnosis of Amyand hernia with high accuracy and confidence.

4.
Commun Biol ; 4(1): 102, 2021 01 22.
Article in English | MEDLINE | ID: mdl-33483601

ABSTRACT

Pro-inflammatory M1 macrophage polarization is associated with microbicidal and antitumor responses. We recently described APOBEC3A-mediated cytosine-to-uracil (C > U) RNA editing during M1 polarization. However, the functional significance of this editing is unknown. Here we find that APOBEC3A-mediated cellular RNA editing can also be induced by influenza or Maraba virus infections in normal human macrophages, and by interferons in tumor-associated macrophages. Gene knockdown and RNA_Seq analyses show that APOBEC3A mediates C>U RNA editing of 209 exonic/UTR sites in 203 genes during M1 polarization. The highest level of nonsynonymous RNA editing alters a highly-conserved amino acid in THOC5, which encodes a nuclear mRNA export protein implicated in M-CSF-driven macrophage differentiation. Knockdown of APOBEC3A reduces IL6, IL23A and IL12B gene expression, CD86 surface protein expression, and TNF-α, IL-1ß and IL-6 cytokine secretion, and increases glycolysis. These results show a key role of APOBEC3A cytidine deaminase in transcriptomic and functional polarization of M1 macrophages.


Subject(s)
Cytidine Deaminase/metabolism , Macrophages/metabolism , Nuclear Proteins/metabolism , Proteins/metabolism , RNA Editing , Humans , Primary Cell Culture
5.
Can J Physiol Pharmacol ; 99(3): 332-347, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32721224

ABSTRACT

Hepatic encephalopathy depicts the cluster of neurological alterations that occur during acute or chronic hepatic injury. Hyperammonemia, inflammatory injury, and oxidative stress are the main predisposing factors for the direct and indirect changes in cerebral metabolism causing encephalopathy. The aim of this study was to evaluate the possible synergistic effect between aminoguanidine (AG; 100 mg/kg, p.o.) and l-carnosine (CAR; 200 mg/kg, p.o.) on hepatic encephalopathy that was induced by thioacetamide (TAA; 100 mg/kg, i.p.) administered three times weekly for six weeks. Behavioral changes, biochemical parameters, histopathological analysis, and immunohistochemical and ultrastructural studies were conducted 24 h after the last treatment. Combining AG with CAR improved TAA-induced locomotor impairment and motor incoordination evidenced by reduced locomotor activity and decline in motor skill performance, as well as ameliorated cognitive deficits. Moreover, both drugs restored the levels of serum hepatic enzymes and serum and brain levels of ammonia. In addition, the combination significantly modulated hepatic and brain oxidative stress biomarkers, inflammatory cytokines, and cleaved caspase-3 expression. Furthermore, they succeeded in activating nuclear erythroid 2-related factor 2 (Nrf2) expression and heme oxygenase-1 (HO-1) activity and ameliorating markers of hepatic encephalopathy, including hepatic necrosis and brain astrocyte swelling. This study shows that combining AG with CAR exerted a new intervention for hepatic and brain damage in hepatic encephalopathy due to their complementary antioxidant, anti-inflammatory effects and hypoammonemic effects via Nrf2/HO-1 activation and NO inhibition.


Subject(s)
Carnosine/therapeutic use , Guanidines/therapeutic use , Hepatic Encephalopathy/prevention & control , Thioacetamide , Ammonia/metabolism , Animals , Behavior, Animal , Brain/pathology , Brain Chemistry/drug effects , Drug Synergism , Hepatic Encephalopathy/chemically induced , Hepatic Encephalopathy/psychology , Liver/pathology , Liver Function Tests , Male , Motor Activity/drug effects , Motor Skills/drug effects , Rats , Rats, Wistar
7.
Z Rheumatol ; 78(4): 365-371, 2019 May.
Article in English | MEDLINE | ID: mdl-30874932

ABSTRACT

Hughes-Stovin syndrome (HSS), characterized by the combination of multiple pulmonary artery aneurysms and deep vein thrombosis, is a rare and an under-recognized clinical entity with less than 40 published cases in English medical literature. Vascular venous thrombotic events, as occurring in the course of Behçet's disease (BD), are also described in HSS, e. g., vena cava, intra-cardiac, jugular vein, iliac vein, femoral vein, and dural sinus thrombosis. We describe a 35-year-old man with HSS showing classical features of the syndrome in the form of recurrent thrombophlebitis of the lower limb veins, pulmonary arterial aneurysms, and left lower limb ischemia with extensive arterial tree involvement. The patient presented with critical arterial ischemia in the left lower limb together with aortic and left common iliac artery thrombosis, occlusion of the left superficial femoral artery, and occlusion of both lower limb arteries. Urgent vascular surgeries were carried out for limb salvage. Shortly after, the patient started on pulse corticosteroid/cyclophosphamide therapy, followed by monthly cyclophosphamide for 1 year, with much improvement. We discuss arterial involvement in HSS and similarities of HSS and BD regarding thrombotic events. We summarize the current management options of HSS.


Subject(s)
Aneurysm , Behcet Syndrome , Pulmonary Embolism , Vasculitis , Adult , Aneurysm/complications , Behcet Syndrome/complications , Behcet Syndrome/diagnosis , Diagnosis, Differential , Humans , Male , Pulmonary Artery/pathology , Pulmonary Embolism/complications , Thromboembolism , Vasculitis/complications , Vasculitis/diagnosis
8.
Reumatismo ; 70(2): 85-91, 2018 Jul 06.
Article in English | MEDLINE | ID: mdl-29976042

ABSTRACT

The aim was to explore possible correlations of antibodies to extractable nuclear antigens (ENA) with clinical manifestations and disease activity indices in systemic lupus erythematosus (SLE) patients. A total of 70 consecutive SLE patients (64 females) were included. Disease activity was assessed by SLE activity index (SLEDAI), and British Isles Lupus Assessment Group (BILAG). Anti-Ro/SSA correlated positively with, headache (r=0.24, p=0.04), blurring of vision (r=0.25, p=0.03) and SLEDAI (r=0.25, p=0.04) and negatively with C3 (r=-0.35, p=0.003). Anti-Ro/SSA correlated with anti La/SSB antibodies (r=0.69, p<0.001), but not with anti-DNA, anti-RNP and anti-Sm antibodies. Anti-La/SSB antibodies correlated with headache (r=0.26, p=0.03), SLEDAI (r=0.25, p=0.03) and negatively with C3 (r=-0.34, p=0.004). Anti-La/SSB did not correlate with anti-RNP or anti-Sm antibodies. Anti-Sm antibodies correlated with disease duration (r=0.34, p=0.003), 24 hours urinary proteins (r=0.31, p=0.008), SLEDAI (r=0.31, p=0.009), BILAG renal score (r=0.29, p=0.02) and negatively with age at onset (r=-0.27, p=0.02), WBCs (r=-0.29, p=0.014) and C4 (r=-0.25, p=0.049). In multivariate analyses, anti-Ro/SSA antibodies remained associated with headache, blurring of vision and C3 and anti-La/SSB antibodies remained associated with C3 and with headache. Anti-Sm antibodies were independently associated with disease duration and total SLEDAI scores, while anti-RNP antibodies remained significantly associated with BILAG mucocutaneous scores only. Antibodies to ENAs are associated with clinical aspects of SLE and may play a role in the assessment of disease activity. Insight into these ENAs may lead to new approaches to diagnostic testing, accurate evaluation of disease activity and lead to target approach for SLE.


Subject(s)
Antibodies, Antinuclear/blood , Autoantigens/immunology , Lupus Erythematosus, Systemic/immunology , Ribonucleoprotein, U1 Small Nuclear/immunology , Ribonucleoproteins/immunology , snRNP Core Proteins/immunology , Adult , Autoantigens/chemistry , Cross-Sectional Studies , Female , Humans , Lupus Erythematosus, Systemic/blood , Male , Middle Aged , Ribonucleoprotein, U1 Small Nuclear/chemistry , Ribonucleoproteins/chemistry , Severity of Illness Index , Solubility , Symptom Assessment , snRNP Core Proteins/chemistry , SS-B Antigen
9.
Can J Physiol Pharmacol ; 95(4): 427-436, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28157387

ABSTRACT

The present study aimed to evaluate the effect of trigonelline (TRG) on the hepatic complications associated with high-fat high-fructose (HFHF) diet-induced insulin resistance (IR) in rats. IR was induced by giving a saturated fat diet and 10% fructose in drinking water to rats for 8 weeks. Insulin-resistant rats were orally treated with TRG (50 and 100 mg/kg), sitagliptin (SIT; 5 mg/kg), or a combination of TRG (50 mg/kg) and SIT (5 mg/kg) for 14 days. Liver homogenates were used for assessment of hepatic lipids, oxidative stress biomarkers, and inflammatory cytokines. Histopathological and DNA cytometry examinations were carried out for hepatic and pancreatic tissues. Hepatic tissues were examined using Fourier-transform infrared spectroscopy for assessment of any molecular changes. Results of the present study revealed that oral treatment of insulin-resistant rats with TRG or TRG in combination with SIT significantly decreased homeostatic model assessment of IR, hepatic lipids, oxidative stress biomarkers, and the inflammatory cytokines. TRG or TRG in combination with SIT ameliorated the histopathological, DNA cytometry, and molecular alterations induced by a HFHF diet. Finally, it can be concluded that TRG has beneficial effects on the hepatic complications associated with IR due to its hypoglycemic effect and antioxidant potential.


Subject(s)
Alkaloids/therapeutic use , Antioxidants/therapeutic use , Hypoglycemic Agents/therapeutic use , Metabolic Syndrome/complications , Non-alcoholic Fatty Liver Disease/drug therapy , Sitagliptin Phosphate/therapeutic use , Animals , Biomarkers/analysis , Blood Glucose/analysis , Cytokines/analysis , Diet, Carbohydrate Loading/adverse effects , Diet, High-Fat/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical , Drug Therapy, Combination , Humans , Lipids/analysis , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Metabolic Syndrome/etiology , Non-alcoholic Fatty Liver Disease/etiology , Oxidative Stress/drug effects , Rats , Rats, Wistar
10.
Data Brief ; 5: 439-46, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26594654

ABSTRACT

This paper contains data to establish the optimal standard regimen and predicting the response to docetaxel therapy (Moawad, 2014) [1]. Docetaxel has been in use for over a decade without demonstrating data indicates a predictable response in the treatment of cancer. Data of puzzling response to docetaxel therapy was due to its cell cycle specific effect. Although several administered schedules were investigated, the relative therapeutic advantage of high versus low doses has not been identified yet. Also the antitumor target of docetaxel has not yet been identified to optimize therapy by predicting the response of patients prior to therapy to provide a protection against treatment failure. In the present paper, we demonstrate the data used to optimize docetaxel therapy and investigate the possibility of predicting for the first time the antitumor target of docetaxel.

11.
Reumatismo ; 67(2): 68-77, 2015 Sep 16.
Article in English | MEDLINE | ID: mdl-26492965

ABSTRACT

Hip disorders in a pediatric population are a diagnostic challenge. The aim of the study is to assess the role of magnetic resonance imaging (MRI) in the evaluation of non-traumatic hip disorders in a series of Egyptian patients and to review the literature on the most common hip conditions. Seventy two consecutive patients [40 males (55.6%) and 32 females (44.4)] with acute onset of hip complaints unrelated to trauma or falls were recruited. All patients underwent an initial full clinical assessment and blood tests as well as contrast enhanced MRI of both hips. The most common diagnosis in this group of Egyptian patients was transient synovitis in 29 (40.3%) cases, followed by seronegative enthesopathy and arthropathy syndrome in 8 (11.1%), septic arthritis in 10 (13.9%), tuberculous arthritis in 4 (5.6%), sickle-cell disease in 7 (9.7%), complicated with septic arthritis in 3 (4.2%), transient bone marrow edema (BME) in 3 (4.2%), osteomyelitis in 2 (2.8%), osteosarcoma in 2 (2.8%), sciatic nerve injury in 1 (1.4%), leukemia with BME in 1 (1.4%), coxa vara of both hips and L5/S1 facet joint ankylosis in 1 (1.4%), and a benign bone cyst in 1 (1.4%). MRI studies showed hip effusion in a total of 51 patients (70.8%), joint space narrowing in 9 (12.5%), and BME in 15(20.8%). MRI is a sensitive tool for assessing hip disorders in a pediatric population and can play an important role in both diagnosis and management of different hip disorders, irrespective of the underlying pathology.


Subject(s)
Hip Joint/diagnostic imaging , Joint Diseases/diagnostic imaging , Magnetic Resonance Imaging , Anemia, Sickle Cell/complications , Arthritis/diagnostic imaging , Arthritis/epidemiology , Child , Child, Preschool , Comorbidity , Egypt/epidemiology , Enthesopathy/diagnostic imaging , Enthesopathy/epidemiology , Female , Follow-Up Studies , Hemarthrosis/diagnostic imaging , Hemarthrosis/epidemiology , Hemarthrosis/etiology , Humans , Joint Diseases/epidemiology , Male , Prospective Studies , Synovitis/diagnostic imaging , Synovitis/epidemiology
12.
J Gastrointest Cancer ; 46(4): 380-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26346504

ABSTRACT

OBJECTIVES: This study aims in optimizing and predicting the in-vivo activity of AT9283 as a monotherapy and evaluating its combination with paclitaxel. DESIGN AND METHODS: The effectiveness of AT9283 was examined in several mouse models engrafted with BCR-ABL(+) leukemic, human multiple myeloma (MM), and human colorectal carcinoma (HCT116) cells. Dose modeling was performed by analyzing previously published data of AT9283 cancer growth inhibition in vivo. The effects of 2 cycles (7.5-12.5 mg/kg AT9283 twice daily, 5 days/week), 4 cycles (45 mg/kg AT9283 once daily, twice/week), and 3 cycles (10 mg/kg AT9283 twice daily for 5 days or 12.5 mg/kg paclitaxel once/week followed by 5 mg/kg AT9283 twice daily for 4 days) on xenograft growth were quantified to identify the energy yield associated with the different doses. RESULTS: The continuous infusion regimens (5 days/week) used in the mice engrafted with BCR-ABL+ cells were more efficient than the regimens with twice weekly drug administration used in the mice engrafted with MM cells. The energy yield of the treatment regimen used in the BCR-ABL(+) model was perfectly correlated (r = 1) with the AT9283 dose logarithm. An efficient dose-energy model with a perfect fit (R (2) = 1) estimating the energy yield achieved by the different AT9283 doses in optimal regimens was established with the aim of being able to administer patient-specific AT9283 doses. In the HCT116 model, the predicted response to AT9283 monotherapy was nearly identical to the actual response. The regimen combining paclitaxel (1050 mg/L) with low-dose AT9283 (3360 mg/L) used in the HCT116 model was equivalent to an optimal regimen of a higher dose of AT9283 (11,332 mg/L) alone. CONCLUSIONS: Administering AT9283 via continuous infusion optimizes treatment, while combining it with paclitaxel significantly reduces the required AT9283 dose for the advanced-stage tumors with low mitotic index.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Benzimidazoles/pharmacology , Multiple Myeloma/drug therapy , Paclitaxel/pharmacology , Protein Kinase Inhibitors/pharmacology , Urea/analogs & derivatives , Animals , Cell Proliferation/drug effects , Drug Therapy, Combination , Humans , K562 Cells , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Multiple Myeloma/pathology , Urea/pharmacology , Xenograft Model Antitumor Assays
13.
J Gastrointest Cancer ; 46(3): 272-83, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25985771

ABSTRACT

INTRODUCTION: This research aims to optimize and predict the effectiveness of imatinib mesylate (imatinib) in tumors expressing platelet-derived growth factors (PDGF-AA, BB), kit/stem cell factor (SCF) ligands and their respective receptors (PDGFR-α, PDGFR-ß, and c-kit). MATERIAL AND METHODS: Samples of normal primary human T cells were incubated with graded concentrations of 1-5 µM imatinib. The energy yield by imatinib doses in those samples was identified in H-thymidine proliferation assay as described before in earlier studies. Tumor models of human pancreatic adenocarcinoma L3.6pl (PDGFAA/PDGFR-α-positive and KIT-negative), human male gonad Leydig tumor cells MA10 (PDGF-AA/PDGFR-α- positive and KIT-positive), human small-cell lung cancer [H209 (KIT-positive), NCI-H526 (PDGFR ß-positive and KIT-positive), and NCI-H82 (PDGFR ß-positive and KIT-negative)], and human neuroblastoma SMS-KCNR (PDGF-BB/PDGFR-ß-positive and KIT-positive) in athymic nude mice were used. The antitumor activity of different doses of imatinib in different regimens in those xenografts was predicted as described before in earlier studies. RESULTS: The energy yield by drug doses was perfectly logarithmic correlated (r = 1) with the drug dose. An efficient dose-energy model with perfect fit (R = 1) estimating the energy yield by imatinib doses has been established to administer the personalized dose. Predictions for the antitumor activity of imatinib in those xenografts using the dose-energy model and the histologic grade of the control animals were 100 % identical to those actually induced. CONCLUSION: The effect of imatinib is transient and reversible, reduces tyrosine phosphorylation of tumor-derived PDGFR-α, PDGFR-ß, and c-kit without affecting their levels of expression. A resumption of tumor growth nearly identical to the growth prior to therapy should be expected whenever the treatment is stopped. Tumors of PDGF-AA/PDGFR-α exhibit significant resistance to imatinib which requires administering imatinib three times a day, whereas resistance of tumors of PDGF-BB/PDGFR-ß or KIT-positive is relatively lower which requires administering imatinib two times a day only to produce an actual inhibition 100 % identical to that predicted for tumor growth.


Subject(s)
Antineoplastic Agents/therapeutic use , Imatinib Mesylate/therapeutic use , Platelet-Derived Growth Factor/metabolism , Receptor, Platelet-Derived Growth Factor beta/metabolism , Stem Cell Factor/metabolism , Animals , Antineoplastic Agents/metabolism , Humans , Imatinib Mesylate/metabolism , Ligands , Mice , Xenograft Model Antitumor Assays
14.
Indian J Clin Biochem ; 29(4): 442-51, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25298625

ABSTRACT

The purpose of this study is optimizing the l-arginine (l-Arg) doses on the basis of chemical structure in regional accessible tumor therapy to settle down a new protocol for the treatment of cancer. (3)H-thymidine-based cell proliferation assay was performed in vitro on tumor cell lines of fibrosarcoma (FS), lymphosarcoma-ascitic and on normal cell line of NIH 3T3 after treatment with different concentrations of l-Arg in phosphate buffered saline (PBS). The cultures were harvested after 22 h and the incorporated radioactivity was counted to identify their histologic grades as described in earlier studies. In vivo therapy of murine tumors was conducted where FS cells injected subcutaneously at ventro-lateral position of mice. Various drug delivery schedules were injected into the centre of tumor base, once a day for 4 days. Tumor diameter and survivals were monitored where the day of sacrifice was considered for monitoring the survival period. By identifying the histologic grades of the treated cultures in vitro and in vivo by different concentrations of l-Arg, the corresponding energy of such concentrations were determined. An efficient model with a good fit (R(2) = 0.98) was established to describe the energy yield by l-Arg dose. The equivalence between the tumor histologic grade and energy of the l-Arg dose delivered in saline (PBS) environment is the optimum condition for regional tumor therapy achieves higher survival rate. The selective cytotoxicity to tumor cells with minimal damage to normal cells by l-Arg due to its chemical structure suggests to be considered the most promising drug for regional therapy of the accessible tumors like breast cancers of early stage with no distant metastasis.

15.
Indian J Clin Biochem ; 29(4): 491-5, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25298631

ABSTRACT

The goal of this work is to determine the role of the autoimmune cells in multiple sclerosis (MS) induction and the immunomodulatory mechanism of therapy with tyrosine kinase inhibitors (TKIs) in MS attenuation. Samples (5 × 10(5) cells per well) of C6 and primary rat astrocytes were stimulated with 10 ng/mL of platelet-derived growth factor (PDGFbb) as a positive control forming a mouse model of MS. PDGFbb was added to the astrocytes in the absence or presence of 0.1 and 1 µM of imatinib. Proliferation of C6 and primary rat astrocytes samples were assessed for samples staging by the addition of 1 µCi of (3)H-thymidine per well. Samples of RAW 264.7 cells were stimulated for 48 h with 10 ng/mL of PDGFbb in the absence or presence of 0.1 and 1 µM of sorafenib. Tumour necrotic factor (TNF) levels in culture supernatants from RAW 264.7 cells were measured by ELISA. The histologic grade (HG) and the level of TNF of the mouse model of MS was 1/5 and 5 times respectively of those in the control one to clarify that MS induction is due to a major decrease in HG inversely proportional to the accompanied increase in TNF level perpetuating local inflammation and demyelination in MS lesion. The addition of 0.1 and 1 µM doses of imatinib increased HG of the mouse model of MS by 6 and 11 times respectively while 0.1 and 1 µM doses of sorafenib decreased TNF level to be 1/2 and 1/5 of that in the mouse model of MS respectively restoring normal rate of TNF level of normal lesion to show that HGand TNF level would be strongly inversely correlated (r = -0.99) in attenuating MS effectively by TKIs therapy but not in an inverse proportion as in MS induction.

16.
Mutat Res ; 770: 120-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25771878

ABSTRACT

The purpose of this research is optimizing and predicting the potent activity of docetaxel through an efficient regimen to settle down a new protocol for the treatment of cancer. Effectiveness of docetaxel was examined in vivo in several mouse models engrafted either subcutaneously or intravenously with several types of cell lines. The effects of 147-5040mg/L of docetaxel in treatments of different regimens in those xenograft growths were monitored and quantified to identify energy of those doses as described before in earlier studies. Mock processes were performed on untreated groups of mice for controls. Docetaxel had significant influence on all sizes of treated tumors compared to the control animals. The longer the induced tumor doubling time intraday to more than half the time period from the start of therapy to the time of delivery of the dose, the higher the energy of docetaxel doses and hence the effectiveness of the treatment and vice versa. The energy yield by drug doses in optimal standard regimens was perfectly power correlated (r=1) with the drug dose. An efficient dose-energy model with a perfect fit (R(2)=1) estimating the energy yield by docetaxel doses in optimal standard regimens has been established to administer the personalized dose. Administration of docetaxel doses should be patient-specific and sufficient for the suggested regimen. Time periods from the start of therapy to the time of dose delivery of the efficient regimen are shorter than twice the tumor doubling time intraday on time of dose delivery. Patients with tumors of lower mitotic index may particularly benefit more from optimal standard regimens, whereas metronomic regimens would be more efficient in patients with tumors of higher mitotic index that need lower doses of docetaxel.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/standards , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms/drug therapy , Taxoids/administration & dosage , Animals , Cell Division/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Docetaxel , Dose-Response Relationship, Drug , Drug Administration Schedule , Hep G2 Cells , Humans , Mice , Neoplasms/diagnosis , Neoplasms/pathology , Prognosis , Reference Standards , Treatment Outcome , Xenograft Model Antitumor Assays
17.
Metab Brain Dis ; 29(2): 533-40, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24248635

ABSTRACT

Identifying the optimal dose of ritonavir therapy overcomes the chemical resistance may exhibit in some cases due to poor prognosis of imprecise staging. Dose modeling was performed by analyzing previously published data of ritonavir cancer growth inhibition in vitro and in vivo. In-vitro 3H-Thymidine-based cell proliferation assay was performed on samples of the GL15 cell line incubated with 0, 1, 10 and 100 µ M of ritonavir. Proliferation inhibition was quantified to identify energy of the used doses as described before in earlier studies. Models involving in-vivo growth of established breast cancer tumor (MDA-MB-231), KSIMM tumor and EL4-T cell thymomas in mice were used. The effects of 40 mg/kg/day for 52 days, 30 mg/kg/day for 15 days and 8.8 mg/mouse/day for about 1 week of ritonavir in those xenograft growths respectively were monitored and quantified to identify energy of those doses as described before in earlier studies. Ritonavir demonstrated an in-vitro reduction in proliferation rate in dose dependent manner. The energy of the in-vitro influences following ritonavir therapy were perfectly correlated (r = 1) with ritonavir dose, allowed to establish an efficient energy-model with a perfect fit (R2=1) describes the energy yield by ritonavir doses, enables to administer the appropriate dose. Ritonavir had also a significant influence in-vivo on all sizes of treated tumors compared to the control animals such that the energy yield by the administered drug as derived from the energy-model was 100% identical to the induced influence in tumor energy. The in-vitro determination of inhibition to proliferation by ritonavir doses is useful to characterize the response of cancer to ritonavir therapy targeting patient-personalized cancer medicine. The molecular method of response determination by 3H-TDR incorporation and ritonavir dose-energy model are reliable to avoid chemo-resistance by identifying the optimal dosing regimens and schedules prior therapy allowing the use of much lower dose of ritonavir and thus decreases the drug side effects and risks of relapse.


Subject(s)
Analgesics/administration & dosage , Breast Neoplasms/drug therapy , Ritonavir/administration & dosage , Xenograft Model Antitumor Assays/methods , Animals , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Dose-Response Relationship, Drug , Female , Male , Mice , Mice, Inbred C57BL , Mice, Nude
18.
Cancer Nanotechnol ; 3(1-6): 37-46, 2012.
Article in English | MEDLINE | ID: mdl-26069495

ABSTRACT

Clinical staging model at the nanoscale (CSMN) has been performed on adenocarcinoma of the colon from five patients ranging in age from 57 to 76 years based on determining their malignant size, estimating their doubling time through imaging techniques, and thus by measuring the average of the tumor nanoparticle doubling time their histologic grade has been identified at the nanoscale. Another two pathologic staging models at the nanoscale PSM [H-3] N and PSM [C-14] N for evaluating the histologic grade have been performed on those tumors based on the in vitro measuring of cell proliferating of tumor slices by either of the [H-3] tritiated and [C-14] thymidine incorporation hypothesizing in PSM [H-3] N that the malignant fraction of the detected tumor is the unlabeled fraction of the tumor by the [H-3] tritiated thymidine, while positing in PSM [C-14] N that the percentage increase of the tumor nanoparticle doubling time than that of the normal tissue at the Natural Background Radiation is equivalent to the percentage deficit of [C-14] incorporation in tumor cells. The consistency of results of the three staging models has been analyzed using ANOVA. Identical histologic grades have been identified by the three staging models for tumors of early stages (p < 0.0001). While for those of advanced disease, evaluation of the histologic grade was identical by CSMN and PSM [H-3] N only (p < 0.0001), whereas was invalid by PSM [C-14] N.

19.
Syst Synth Biol ; 6(3-4): 61-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-24294340

ABSTRACT

The goal of this work is to optimize production of bio-ethanol by fermentation through regulating yeast growth energy (YGE), and provide the mechanism of ethanol production from food-waste leachate (FWL) using yeast (S. cerevisiae) as inoculums to be predictable and controllable. The wide range of reduced sugar concentration (RSC) which is commonly administered from low (35 g per liter) to very high (100 g per liter) is responsible for costs increasing besides risks of FWL contamination and death of yeast cells. A mathematical model is presented to describe yeast growth energy (YGE) due to RSC doses along with predicting the amounts of ethanol yield by each dose to identify the optimum one. Simulations of the presented model showed that YGE, energy intake (EI), and their produced ethanol energy (PEE) are always balanced during fermentation process according to the law of conservation of energy. For a better fermentation rate in a continuous process and a large-scale production; YGE should be less than half of EI and more than its quarter (i.e. [Formula: see text]) which keeps the residual energy less than YGE to avoid risks of osmotic stresses or aging of cells allowing the survival of all yeast cells as long as possible to maximize ethanol production and decrease productivity costs.

20.
BMC Ecol ; 11: 24, 2011 Oct 10.
Article in English | MEDLINE | ID: mdl-21985688

ABSTRACT

BACKGROUND: Sand fly saliva can drive the outcome of Leishmania infection in animal models, and salivary components have been postulated as vaccine candidates against leishmaniasis. In the sand fly Phlebotomus papatasi, natural sugar-sources modulate the activity of proteins involved in meal digestion, and possibly influence vectorial capacity. However, only a handful of studies have assessed the variability of salivary components in sand flies, focusing on the effects of environmental factors in natural habitats. In order to better understand such interactions, we compared the expression profiles of nine P. papatasi salivary gland genes of specimens inhabiting different ecological habitats in Egypt and Jordan and throughout the sand fly season in each habitat. RESULTS: The majority of investigated genes were up-regulated in specimens from Swaymeh late in the season, when the availability of sugar sources is reduced due to water deprivation. On the other hand, these genes were not up-regulated in specimens collected from Aswan, an irrigated area less susceptible to drought effects. CONCLUSION: Expression plasticity of genes involved with vectorial capacity in disease vectors may play an important epidemiological role in the establishment of diseases in natural habitats.


Subject(s)
Genes, Insect , Phlebotomus/genetics , Seasons , Animals , Carbohydrate Metabolism , Droughts , Egypt , Jordan , Leishmania/physiology , Phlebotomus/parasitology , Salivary Glands , Up-Regulation
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