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1.
Int J Mol Sci ; 25(5)2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38473875

ABSTRACT

The interplay between predator and prey has catalyzed the evolution of venom systems, with predators honing their venoms in response to the evolving resistance of prey. A previous study showed that the African varanid species Varanus exanthematicus has heightened resistance to snake venoms compared to the Australian species V. giganteus, V. komodoensis, and V. mertensi, likely due to increased predation by sympatric venomous snakes on V. exanthematicus. To understand venom resistance among varanid lizards, we analyzed the receptor site targeted by venoms in 27 varanid lizards, including 25 Australian varanids. The results indicate an active evolutionary arms race between Australian varanid lizards and sympatric neurotoxic elapid snakes. Large species preying on venomous snakes exhibit inherited neurotoxin resistance, a trait potentially linked to their predatory habits. Consistent with the 'use it or lose it' aspect of venom resistance, this trait was secondarily reduced in two lineages that had convergently evolved gigantism (V. giganteus and the V. komodoensis/V. varius clade), suggestive of increased predatory success accompanying extreme size and also increased mechanical protection against envenomation due to larger scale osteoderms. Resistance was completely lost in the mangrove monitor V. indicus, consistent with venomous snakes not being common in their arboreal and aquatic niche. Conversely, dwarf varanids demonstrate a secondary loss at the base of the clade, with resistance subsequently re-evolving in the burrowing V. acanthurus/V. storri clade, suggesting an ongoing battle with neurotoxic predators. Intriguingly, within the V. acanthurus/V. storri clade, resistance was lost again in V. kingorum, which is morphologically and ecologically distinct from other members of this clade. Resistance was also re-evolved in V. glebopalma which is terrestrial in contrast to the arboreal/cliff dwelling niches occupied by the other members of its clade (V. glebopalma, V. mitchelli, V. scalaris, V. tristis). This 'Russian doll' pattern of venom resistance underscores the dynamic interaction between dwarf varanids and Australian neurotoxic elapid snakes. Our research, which included testing Acanthophis (death adder) venoms against varanid receptors as models for alpha-neurotoxic interactions, uncovered a fascinating instance of the Red Queen Hypothesis: some death adders have developed more potent toxins specifically targeting resistant varanids, a clear sign of the relentless predator-prey arms race. These results offer new insight into the complex dynamics of venom resistance and highlight the intricate ecological interactions that shape the natural world.


Subject(s)
Lizards , Animals , Lizards/physiology , Australia , Elapidae , Snake Venoms , Venomous Snakes , Russia , Elapid Venoms
4.
Am J Mens Health ; 13(6): 1557988319891350, 2019.
Article in English | MEDLINE | ID: mdl-31775566

ABSTRACT

Preseason in rugby union is a period of intensive training where players undergo conditioning to prepare for the competitive season. In some cases, this includes modifying body composition through weight gain or fat loss. This study aimed to describe the macronutrient intakes of professional rugby union players during pre-season training. It was hypothesized that players required to gain weight would have a higher energy, carbohydrate and protein intake compared to those needing to lose weight. Twenty-three professional rugby players completed 3 days of dietary assessment and their sum of eight skinfolds were assessed. Players were divided into three groups by the team coaches and medical staff: weight gain, weight maintain and weight loss. Mean energy intakes were 3,875 ± 907 kcal·d-1 (15,965 ± 3,737 kJ·d-1) (weight gain 4,532 ± 804 kcal·d-1; weight maintain 3,825 ± 803 kcal·d-1; weight loss 3,066 ± 407 kcal·d-1) and carbohydrate intakes were 3.7 ± 1.2 g·kg-1·d-1 (weight gain 4.8 ± 0.9 g.kg-1·d-1; weight maintain 2.8 ± 0.7 g·kg-1·d-1; weight loss 2. 6 ± 0.7 g·kg-1·d-1). The energy and carbohydrate intakes are similar to published intakes among rugby union players. There were significant differences in energy intake and the percent of energy from protein between the weight gain and the weight loss group.


Subject(s)
Athletes/statistics & numerical data , Athletic Performance/physiology , Body Composition/physiology , Energy Intake/physiology , Football , Body Mass Index , Cross-Sectional Studies , Humans , Male , New Zealand , Physical Education and Training
5.
J Anim Ecol ; 88(5): 757-767, 2019 05.
Article in English | MEDLINE | ID: mdl-30828806

ABSTRACT

Foraging modes (ambush vs. active foraging) are often correlated with a suite of morphological, physiological, behavioural and ecological traits known as the "adaptive syndrome" or "syndrome hypothesis." In snakes, an ecological correlate often reported in the literature is that ambush-hunting snakes have a higher relative meal size compared to actively foraging snakes which feed on smaller prey items. This "large meal versus small meal" feeding hypothesis between ambush and active foragers has become a widely accepted paradigm of snake feeding ecology, despite the fact that no rigorous meta-analysis has been conducted to support this generalization. We conducted a phylogenetically explicit meta-analysis, which included ca. 100 species, to test this paradigm of snake feeding ecology. We gathered data on prey size by inducing regurgitation by palpation in free-ranging snakes and by examining the stomach contents of preserved museum specimens. When we found prey, we recorded both snake and prey mass to estimate relative prey mass (prey mass/snake mass). We also reviewed published studies of snake feeding ecology to gather similar information for other species. Ambush and active foragers did not differ in minimum or average meal size but the maximum meal sizes consumed by ambush-foraging snakes were larger than the maximum meal sizes eaten by active foragers. This results in ambush-foraging snakes consuming a significantly wider range of meal sizes, rather than being large meal specialists compared to active foragers. We argue that ambush foragers evolved to be more opportunistic predators because they encounter prey less frequently compared to active foragers. This hypothesis is further supported by the fact that ambush foragers also exhibited marginally wider diet breadths, consuming a broader range of prey types in comparison with active foragers. Our study challenges aspects of the foraging syndrome as it is currently conceived, and our results have important implications for our understanding of how foraging mode has shaped the behaviour and physiology of ambush-foraging snakes.


Subject(s)
Predatory Behavior , Snakes , Animals , Diet , Ecology , Feeding Behavior
6.
Clin Transl Oncol ; 21(4): 499-504, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30229391

ABSTRACT

PURPOSE: The standard treatment for patients with stage III non-small cell lung cancer (NSCLC), unsuitable for resection and with good performance, is definitive radiotherapy with cisplatin-based chemotherapy. Our aim is to evaluate the effect of the maximum value of standardized uptake values (SUVmax) of the primary tumor in positron emission tomography-computed tomography (PET/CT) before treatment on complete response (CR) and overall survival. METHODS: The data of 73 stage III NSCLC patients treated with concurrent definitive chemoradiotherapy (CRT) between 2008 and 2017 and had PET/CT staging in the pretreatment period were evaluated. ROC curve analysis was performed to determine the ideal cut-off value of pretreatment SUVmax to predict CR. RESULTS: Median age was 58 years (range 27-83 years) and 66 patients were male (90.4%). Median follow-up time was 18 months (range 3-98 months); median survival was 23 months. 1-year overall survival (OS) rate and 5-year OS rate were 72 and 19%, respectively. Median progression-free survival (PFS) was 9 months; 1-year PFS rate and 5-year PFS rate were 38 and 19%, respectively. The ideal cut-off value of pretreatment SUVmax that predicted the complete response of CRT was 12 in the ROC analysis [AUC 0.699 (0.550-0.833)/P < 0.01] with a sensitivity of 83%, and specificity of 55%. In patients with SUVmax < 12, CR rate was 60%, while, in patients with SUV ≥ 12, it was only 19% (P = 0.002). Median OS was 26 months in patients with pretreatment SUVmax < 12, and 21 months in patients with SUVmax ≥ 12 (HR = 2.93; 95% CI 17.24-28.75; P = 0.087). CR rate of the whole patient population was 26%, and it was the only factor that showed a significant benefit on survival in both univariate and multivariate analyses. CONCLUSION: Pretreatment SUVmax of the primary tumor in PET/CT may predict CR in stage III NSCLC patients who were treated with definitive CRT. Having clinical CR is the only positive predictive factor for prolonged survival.


Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/metabolism , Lung Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Chemoradiotherapy , Female , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Prognosis , ROC Curve , Radiopharmaceuticals/pharmacokinetics , Retrospective Studies , Survival Rate , Treatment Outcome
7.
J Diet Suppl ; 16(4): 443-453, 2019.
Article in English | MEDLINE | ID: mdl-29958049

ABSTRACT

N-acetylcysteine (NAC) supplementation may enhance performance and reduce soreness from acute, repeated-sprint, high-intensity exercise. Our aim was to investigate whether semi-elite rugby union athletes may benefit. In a randomized block design, 17 semi-elite male rugby players were assigned to receive either 1 g oral NAC (n = 8) or placebo (n = 9) for six days. The mean percentage effect of NAC on exercise performance was assessed through completion of a broken bronco exercise test on days 5 and 6 of supplementation. Players self-reported muscle soreness and tolerability to supplements using a modified Muscle Pain and Treatment Satisfaction Questionnaire throughout the supplement duration. NAC produced a likely beneficial performance effect on maximum shuttle sprint time (2.4%; 90% confidence limit ± 4.8%) but was unclear on total time during back-to-back broken bronco tests compared to placebo. NAC had a likely protective effect on subjective muscle soreness during days 1-4 of supplementation (-19% ± 27%) but a very likely harmful effect on days 5 and 6 of supplementation (71% ± 59%). Daily supplementation with 1 g of oral NAC for six days produced no adverse side effects, reduced muscle soreness after one bout of damaging exercise, but increased soreness following the second bout. The performance effects were generally unclear apart from maximal sprint time.


Subject(s)
Acetylcysteine/administration & dosage , Athletes , Football , Myalgia/drug therapy , Physical Functional Performance , Acetylcysteine/adverse effects , Dietary Supplements , Double-Blind Method , Exercise Test , Humans , Male , New Zealand , Placebos , Surveys and Questionnaires
8.
Ann Oncol ; 26(1): 149-156, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25416687

ABSTRACT

BACKGROUND: Docetaxel/cisplatin/infusional 5-fluorouracil (5-FU; DCF) is a standard chemotherapy regimen for patients with advanced gastric cancer (GC). This phase II study evaluated docetaxel/oxaliplatin (TE), docetaxel/oxaliplatin/5-FU (TEF), and docetaxel/oxaliplatin/capecitabine (TEX) in patients with advanced GC. PATIENTS AND METHODS: Patients with metastatic or locally recurrent gastric adenocarcinoma (including carcinoma of the gastro-oesophageal junction) were randomly assigned (1 : 1 : 1) to TE, TEF, or TEX. Each regimen was tested at two doses before full evaluation at optimized dose levels. The primary end point was progression-free survival (PFS). Overall survival (OS), tumour response, and safety were also assessed. A therapeutic index (median PFS relative to the incidence of febrile neutropenia) was calculated for each regimen and compared with DCF (historical data). RESULTS: Overall, 248 patients were randomly assigned to receive optimized dose treatment. Median PFS was longer with TEF (7.66 [95% confidence interval (CI): 6.97-9.40] months) versus TE (4.50 [3.68-5.32] months) and TEX (5.55 [4.30-6.37] months). Median OS was 14.59 (95% CI: 11.70-21.78) months for TEF versus 8.97 (7.79-10.87) months for TE and 11.30 (8.08-14.03) months for TEX. The rate of tumour response (complete or partial) was 46.6% (95% CI 35.9-57.5) for TEF versus 23.1% (14.3-34.0) for TE and 25.6% (16.6-36.4) for TEX. The frequency and type of adverse events (AEs) were similar across the three arms. Common grade 3/4 AEs were fatigue (21%), sensory neuropathy (14%), and diarrhoea (13%). Febrile neutropenia was reported in 2% (TEF), 14% (TE), and 9% (TEX) of patients. The therapeutic index was improved with TEF versus TEX, TE, or DCF. CONCLUSION: These results suggest that TEF is worthy of evaluation as an arm in a phase III trial or as a backbone regimen for new targeted agents in advanced GC. CLINICALTRIALS.GOV: Identifier Trial registration number: NCT00382720.


Subject(s)
Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Fluorouracil/therapeutic use , Organoplatinum Compounds/therapeutic use , Stomach Neoplasms/drug therapy , Taxoids/therapeutic use , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Disease-Free Survival , Docetaxel , Drug Administration Schedule , Female , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Organoplatinum Compounds/adverse effects , Oxaliplatin , Prospective Studies , Stomach Neoplasms/mortality , Taxoids/adverse effects , Treatment Outcome
9.
Clin. transl. oncol. (Print) ; 16(1): 91-95, ene. 2014. tab, ilus
Article in English | IBECS | ID: ibc-127525

ABSTRACT

PURPOSE: We aimed to determine the efficacy and the toxicity of low dose weekly gemcitabine with radiation therapy in medically unfit muscle-invasive bladder cancer patients. METHODS: Twenty-six patients were included into the retrospective analysis. Weekly gemcitabine was administered 75 mg/m(2) with a median dose of 63 Gy radiation therapy. Clinical target volume was defined as the urinary bladder only in conformal treatment planning. RESULTS: Median follow-up was 51 months (range 14-118 months). Complete response rate was 62.5 %. The 5-year local progression-free survival, disease-specific survival and overall survival rates were 40.6, 59.5 and 58.5 %, respectively. Concurrent chemotherapy was continued in 80.7 % of patients without any interruption. Gemcitabine was stopped due to grade 3 thrombocytopenia (n = 1), cardiac angina (n = 1), chronic obstructive pulmonary disease exacerbation (n = 1) or patients' reluctance (n = 2). CONCLUSIONS: Low dose weekly gemcitabine with concurrent radiotherapy is a tolerable regimen and have comparable outcomes with platinum-based combined treatments in muscle-invasive bladder cancer. Prospective randomized trials can help in understanding the safety and efficacy of this treatment specially in medically unfit patients (AU)


No disponible


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Carcinoma, Transitional Cell/therapy , Chemoradiotherapy/methods , Urinary Bladder Neoplasms/therapy , Retrospective Studies , Disease-Free Survival , Kaplan-Meier Estimate , Treatment Outcome , Urinary Bladder Neoplasms/mortality
10.
Clin Transl Oncol ; 16(1): 91-5, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23615982

ABSTRACT

PURPOSE: We aimed to determine the efficacy and the toxicity of low dose weekly gemcitabine with radiation therapy in medically unfit muscle-invasive bladder cancer patients. METHODS: Twenty-six patients were included into the retrospective analysis. Weekly gemcitabine was administered 75 mg/m(2) with a median dose of 63 Gy radiation therapy. Clinical target volume was defined as the urinary bladder only in conformal treatment planning. RESULTS: Median follow-up was 51 months (range 14-118 months). Complete response rate was 62.5 %. The 5-year local progression-free survival, disease-specific survival and overall survival rates were 40.6, 59.5 and 58.5 %, respectively. Concurrent chemotherapy was continued in 80.7 % of patients without any interruption. Gemcitabine was stopped due to grade 3 thrombocytopenia (n = 1), cardiac angina (n = 1), chronic obstructive pulmonary disease exacerbation (n = 1) or patients' reluctance (n = 2). CONCLUSIONS: Low dose weekly gemcitabine with concurrent radiotherapy is a tolerable regimen and have comparable outcomes with platinum-based combined treatments in muscle-invasive bladder cancer. Prospective randomized trials can help in understanding the safety and efficacy of this treatment specially in medically unfit patients.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Carcinoma, Transitional Cell/therapy , Chemoradiotherapy/methods , Deoxycytidine/analogs & derivatives , Urinary Bladder Neoplasms/therapy , Aged , Aged, 80 and over , Deoxycytidine/administration & dosage , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/mortality , Gemcitabine
11.
J Strength Cond Res ; 28(2): 520-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23669819

ABSTRACT

The purpose of this study was to compare fluid balance between a resistance and an aerobic training sessions, in elite rugby players. It is hypothesized that resistance exercise will result in a higher prevalence of overdrinking, whereas during the aerobic session, underdrinking will be more prevalent. As with previous fluid balance studies, this was an observational study. Twenty-six players completed the resistance training session, and 20 players completed the aerobic training session. All players were members of an elite rugby union squad competing in the southern hemisphere's premier competition. For both sessions, players provided a preexercise urine sample to determine hydration status, pre- and postexercise measures of body mass, and blood sodium concentration were taken, and the weight of drink bottles were recorded to calculate sweat rates and fluid intake rates. Sweat patches were positioned on the shoulder of the players, and these remained in place throughout each training session and were later analyzed for sodium concentration. The percentage of sweat loss replaced was higher in the resistance (196 ± 130%) than the aerobic training session (56 ± 17%; p = 0.002). Despite this, no cases of hyponatremia were detected. The results also indicated that more than 80% of players started training in a hypohydrated state. Fluid intake seems to differ depending on the nature of the exercise session. In this group of athletes, players did not match their fluid intakes with their sweat loss, resulting in overdrinking during resistance training and underdrinking in aerobic training. Therefore, hydration strategies and education need to be tailored to the exercise session. Furthermore, given the large number of players arriving at training hypohydrated, improved hydration strategies away from the training venue are required.


Subject(s)
Football/physiology , Physical Conditioning, Human/physiology , Resistance Training , Running/physiology , Water-Electrolyte Balance/physiology , Adolescent , Adult , Body Weight , Drinking , Humans , Hyponatremia/blood , Male , Physical Conditioning, Human/methods , Sodium/analysis , Sodium/blood , Specific Gravity , Sweat/chemistry , Sweating/physiology , Urinalysis , Young Adult
12.
Neoplasma ; 60(1): 19-25, 2013.
Article in English | MEDLINE | ID: mdl-23067212

ABSTRACT

The aim of this study is to evaluate the tolerability and toxicity of adjuvant chemoradiotherapy (CRT) and to analyze the prognosis in patients with operable gastric cancer. The retrospective analysis included 723 patients with operable gastric cancer; stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. The patients' age, sex, tumor localization, Lauren classification, grade and stage of the disease, type of dissection, the toxicity and tolerability status and survival rate were analyzed. All patients were divided into two groups as tolerable group to adjuvant CRT and intolerable group to adjuvant CRT .Among the patient, 73.9% had stage III-IVM0 disease; 61.0% had the intestinal type of gastric cancer, 51.1% had the distal type, and 61.4% had undergone D2 dissections. The number of patients who completed the entire course of the adjuvant CRT was 545 (75.4%).The median follow-up period was 20.8 months (range: 1.5-107 months). Overall Survival (OS) rates were 80% and 52%, while the relapse free survival (RFS) rates were 75% and 48% at 1 and 3 years, respectively.In the univariate analysis of the groups based on the the age defined as <65 or ≥ 65 (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), disease stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), presence or absence of toxicity (p=0.062 / p=0.077) and tolerability of the therapy (p=0.002 / p=0.001). In the cox regression analysis, tumor stage (Hazard Ratio (HR): 0.332; 95% confidence interval (CI): 0.195-0.566; p<0.001), and tolerability (HR: 0.516; 95% CI: 0.305-0.872; p=0.014), were found to be related with the OS. Tumor stage (HR: 0.318; 95% CI: 0.190-0.533; p=<0.001) and tolerability (HR: 0.604; 95% CI: 0.367-0.995; p=0.048) were observed to be statistically significant in terms of the RFS.We have observed that whether a patient can or cannot tolerate adjuvant CRT due to its toxicity is an independent prognostic factor besides the known prognostic factors like tumor stage and Lauren classification. We are of the opinion that the treatment of patients who cannot tolerate adjuvant CRT should be replaced with less toxic adjuvant therapies.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy, Adjuvant , Stomach Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Leucovorin/administration & dosage , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Radiotherapy Dosage , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Rate , Turkey , Young Adult
13.
J BUON ; 17(1): 102-5, 2012.
Article in English | MEDLINE | ID: mdl-22517701

ABSTRACT

PURPOSE: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyse prognostic factors for OS in advanced pancreatic cancer patients treated with first-line palliative chemotherapy with gemcitabine alone or gemcitabine plus cisplatin. METHODS: We retrospectively reviewed 343 locally advanced or metastatic pancreatic cancer patients who were treated with gemcitabine or gemcitabine plus cisplatin as first-line chemotherapy between December 2000 and June 2011. Fifteen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Univariate and multivariate statistical methods were used to determine prognostic factors. RESULTS: Among the 15 variables of univariate analysis, 6 were identified to have prognostic significance: stage (p<0.001), cholestasis (p=0.02), weight loss, prior pancreatectomy, serum CEA level (p<0.001) and serum CA19-9 level (p>0.001). In addition, age, chemotherapy and liver metastasis were of borderline significance (p=0.06). Multivariate analysis (Cox proportional hazard model) included the 6 significant prognostic factors of univariate analysis and showed that stage was independent prognostic factor for OS, as were weight loss, and serum CEA level. CONCLUSION: Stage, weight loss, and serum CEA level were identified as important prognostic factors for OS in advanced pancreatic cancer patients. These findings may also facilitate pretreatment prediction of OS and can be used for selecting patients for treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , CA-19-9 Antigen/blood , Carcinoembryonic Antigen/blood , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/therapeutic use , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/mortality , Prognosis , Proportional Hazards Models , Retrospective Studies , Gemcitabine
14.
Cell Transplant ; 21(7): 1561-75, 2012.
Article in English | MEDLINE | ID: mdl-22526408

ABSTRACT

Bone marrow stromal cell (BMSC) transplantation has shown promise for repair of the spinal cord. We showed earlier that a BMSC transplant limits the loss of spinal nervous tissue after a contusive injury. Here, we addressed the premise that BMSC-mediated tissue sparing underlies functional recovery in adult rats after a contusion of the thoracic spinal cord. Our results reveal that after 2 months BMSCs had elicited a significant increase in spared tissue volumes and in blood vessel density in the contusion epicenter. A strong functional relationship existed between spared tissue volumes and blood vessel density. BMSC-transplanted rats exhibited significant improvements in motor, sensorimotor, and sensory functions, which were strongly correlated with spared tissue volumes. Retrograde tracing revealed that rats with BMSCs had twice as many descending brainstem neurons with an axon projecting beyond the contused spinal cord segment and these correlated strongly with the improved motor/sensorimotor functions but not sensory functions. Together, our data indicate that tissue sparing greatly contributes to BMSC-mediated functional repair after spinal cord contusion. The preservation/formation of blood vessels and sparing/regeneration of descending brainstem axons may be important mediators of the BMSC-mediated anatomical and functional improvements.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Spinal Cord Injuries/therapy , Animals , Blood Vessels/physiopathology , Bone Marrow Cells/cytology , Female , Hot Temperature , Hyperalgesia/physiopathology , Immunohistochemistry , Motor Activity/physiology , Nerve Regeneration , Neurons/metabolism , Neurons/pathology , Rats , Rats, Sprague-Dawley , Sensory Thresholds/physiology , Spinal Cord Injuries/physiopathology
15.
Neoplasma ; 59(3): 297-301, 2012.
Article in English | MEDLINE | ID: mdl-22329849

ABSTRACT

The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Retrospective Studies , Survival Rate , Treatment Outcome , Gemcitabine
16.
Neoplasma ; 59(1): 38-42, 2012.
Article in English | MEDLINE | ID: mdl-22103897

ABSTRACT

This study was aimed to establish clinical efficacy and tolerability of gemcitabine and cisplatin combination in patients with metastatic triple negative breast cancer progressing after anthracycline and taxane based chemotherapies.Thirty-three patients who were given cisplatin and gemcitabine for triple negative and metastatic breast cancer were evaluated retrospectively. A total of 141 cycles were administered with a median 4 cycles per patient. Median follow-up time was 14 months (range, 2-36 months). Objective response rate was 27.3%. Total clinical benefit of the combination was 48.4%. The estimated median progression free survival and median overall survival were 5 months and 14 months, respectively. The most common Grade 3 and 4 toxicity were neutropenia and thrombocytopenia observed in 10 (27.7%) and 9 (24.9%) patients, respectively. The combination of the gemcitabine and cisplatin after taxane/anthracycline is well tolerated and seems to be effective with acceptable toxicity profile.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/secondary , Salvage Therapy , Adult , Aged , Anthracyclines/administration & dosage , Breast Neoplasms/chemistry , Carcinoma, Ductal, Breast/chemistry , Carcinoma, Ductal, Breast/drug therapy , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Drug Evaluation , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neutropenia/chemically induced , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Taxoids/administration & dosage , Thrombocytopenia/chemically induced , Gemcitabine
17.
J BUON ; 16(2): 257-64, 2011.
Article in English | MEDLINE | ID: mdl-21766495

ABSTRACT

PURPOSE: Treatment outcomes and prognostic features of a specific cancer generally come from prospective randomized studies. It seems reasonable to ask the question whether the results of prospective randomized studies entirely reflect the results of the population treated in "real world" practice. Therefore we performed a retrospective cohort analysis in order to find out the efficacy of adjuvant chemotherapy as well as the prognostic factors of our patient population treated in daily practice, and compared these findings with those defined in the prospective studies. METHODS: Data of patients with high risk stage II and all stage III colon cancers treated with adjuvant chemotherapy were retrospectively analyzed. RESULTS: A total of 190 patients were retrospectively analyzed. The rates of T2, T3, and T4 tumors were 4.2, 77.9, and 17.9%, respectively. Over 35% of the patients had stage II disease. Of the 5- fluorouracil (5-FU)-based chemotherapy group (n=141), 15% had a dose reduction because of toxicity and 73% were given the total planned dose and cycles, whereas these rates were 18.5 and 66% for oxaliplatin+5-FU treated group, respectively (p=0.66 and 0.44, respectively). The 3-year disease-free survival (DFS) and 5-year cancer-specific overall survival (OS) for all patients were 69.4 and 73%, respectively. In multivariate analysis, cancer-specific OS showed significant correlation with T stage (p=0.015) and with perineural invasion (p=0.024). Also patients ≥ 65 years old had significantly lower OS (p= 0.003) CONCLUSION: This study is the fi rst to report the efficacy of adjuvant treatment in a curatively resected Turkish colon carcinoma population treated in "real world" practice. Our study showed that the treatment results and the prognostic parameters of Turkish colon carcinoma patients treated in "real world" practice are not different from those of selected patients treated in randomized prospective studies.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Cohort Studies , Colonic Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Multicenter Studies as Topic , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prognosis , Prospective Studies , Randomized Controlled Trials as Topic , Retrospective Studies , Survival Rate
18.
Biomaterials ; 32(26): 6068-79, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21636129

ABSTRACT

Following spinal cord injury, axons fail to regenerate without exogenous intervention. In this study we report that aligned microfiber-based grafts foster robust regeneration of vascularized CNS tissue. Film, random, and aligned microfiber-based conduits were grafted into a 3 mm thoracic rat spinal cord gap created by complete transection. Over the course of 4 weeks, microtopography presented by aligned or random poly-L-lactic acid microfibers facilitated infiltration of host tissue, and the initial 3 mm gap was closed by endogenous cell populations. This bulk tissue response was composed of regenerating axons accompanied by morphologically aligned astrocytes. Aligned fibers promoted long distance (2055 ± 150 µm), rostrocaudal axonal regeneration, significantly greater than random fiber (1162 ± 87 µm) and film (413 ± 199 µm) controls. Retrograde tracing indicated that regenerating axons originated from propriospinal neurons of the rostral spinal cord, and supraspinal neurons of the reticular formation, red nucleus, raphe and vestibular nuclei. Our findings outline a form of regeneration within the central nervous system that holds important implications for regeneration biology.


Subject(s)
Central Nervous System/physiology , Lactic Acid/chemistry , Polymers/chemistry , Spinal Cord Injuries/therapy , Animals , Astrocytes/cytology , Astrocytes/metabolism , Cells, Cultured , Female , Ganglia, Spinal/cytology , Immunohistochemistry , Neurites/metabolism , Polyesters , Rats , Rats, Sprague-Dawley , X-Ray Microtomography
20.
J BUON ; 15(2): 310-3, 2010.
Article in English | MEDLINE | ID: mdl-20658727

ABSTRACT

PURPOSE: Although there are many myths about cancer in Turkey, there is no study evaluating Turkish public's knowledge about cancer. The goals of our research were to: 1) measure the extent of knowledge of cancer among the Turkish public; 2) determine the differences in extent of cancer-related knowledge between participants who have relatives with cancer and those who do not; and 3) determine the sources of knowledge possessed. METHODS: Data were obtained from a total of 415 participants (244 female, 171 male), all of them sitting at the Marmara University Faculty of Medicine Hospital (MUFMH) outpatient clinic waiting area for non-cancer-related reasons. Each participant completed a 3-part questionnaire. Appropriate statistical tests were used for comparison. RESULTS: The mean age was 41 years. Of 415 participants, 65.3% stated that they had one or more cancer patient in their immediate family; 70.1% of the participants had a high-school education or greater. The questionnaire showed that, depending on the question, anywhere from 1.7% to 88.5% of the general public possesses some false information; furthermore, the difference in accuracy between relatives of cancer patients and non-relatives was marginal. Only 3 specific questions, related to the following ideas, rendered answers that were statistically significantly different between these 2 groups: breast cancer is only seen in females (p <0.005), cell phones cause cancer (p <0.001), and cancer is always very painful (p <0.001). CONCLUSION: The proportion of false knowledge about cancer was unacceptably high in our cohort. Broader efforts should be made to inform the Turkish public about cancer.


Subject(s)
Neoplasms , Aged , Diet Therapy , Educational Status , Family , Female , Humans , Knowledge , Male , Middle Aged , Neoplasms/etiology , Neoplasms/pathology , Punishment , Surveys and Questionnaires , Television , Turkey
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