Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status as prognostic factors in lung cancer

Raised serum levels of interleukin 6 (IL-6) have been described in cancer patients. This cytokine mediates the acute phase response and has been also involved in the pathogenesis of cancer cachexia. The objectives of the present study were: (1) to determine the relationships of IL-6 and other cytokines with neoplasia extension, acute phase response and nutritional status, in lung cancer patients; and (2) to establish the prognostic value of serum cytokine levels. A prospective study in which IL-1, IL-2, IL-6, tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have been determined in 66 newly diagnosed lung cancer patients. Nutritional status was assessed objectively. Serum levels of growth hormone (GH), insulin growth factor 1 (IGF-1) and acute phase reactants as C Reactive Protein, alpha1 antitrypsin and ferritine, were determined. Increased IL-6 levels were related to extensive disease, impaired performance status, enhanced acute phase response and malnutrition. Raised serum IL-6 levels, extensive disease, low Karnofsky index, malnutrition, acute phase response and low IFN-gamma were all related to a shorter survival. When assessed by a multivariate analysis, IL-6 kept its independent prognostic value together with age, disease extension, and decreased IFN-gamma serum levels.IL-6 is increased in lung cancer patients, enhances the acute phase response in them, and is correlated with poor nutritional status, impaired performance status and shorter survival.     

Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition?

Leptin is an anorexia inductor peptide produced by adipocytes and related to fat mass. Leptin is also produced by fat under proinflammatory cytokine action. Our objective is to study serum leptin levels in relation to nutritional status and acute phase response in advanced-stage non-small cell lung cancer.Seventy-six patients newly diagnosed of non surgical non-small cell lung cancer before chemotherapy treatment and 30 healthy controls were included. BMI, serum leptin and cholesterol levels and lymphocyte count were decreased in lung cancer patients. Cytokine IL-6, TNF-alpha, sTNF-RII, sIL-2R, IL-12, IL-10 and IFN-gamma, and other acute phase reactants as alpha1 antitrypsin, ferritin, CRP and platelets were all raised in patients, whereas the IL-2 was decreased. We found a direct relationship between leptin and other indicators of the status of nutrition, especially total fat mass. We also found a close relationship between the status of nutrition and the performance status (Karnofsky index). However, serum leptin and nutritional status were inversely correlated with acute phase proteins and proinflammatory cytokines, suggesting a stress-type malnutrition. Although serum leptin levels, nutritional status and Karnofsky index are related to survival, at multivariate analysis they all were displaced by the acute phase reaction markers.These results suggest that cancer anorexia and cachexia are not due to a dysregulation of leptin production. Circulating leptin concentrations are not elevated in weight-losing cancer patients and are inversely related to the intensity of the inflammatory response. In advanced lung cancer patients serum leptin concentrations only depend on the total amount of fat.     

Tissue and serum levels of principal androgens in benign prostatic hyperplasia and prostate cancer

Androgens are considered to play a substantial role in pathogenesis of both benign prostatic hyperplasia (BPH) and prostate cancer. The importance of determination of androgen levels in tissue and serum for cancer progression and prognosis has been poorly understood. The aim of study was to find out hormonal differences in both diseases, their correlations between intraprostatic and serum levels and predicted value of their investigation. Testosterone, dihydrotestosterone, androstenedione and also epitestosterone were determined in prostate tissue from 57 patients who underwent transvesical prostatectomy for BPH and 121 patients after radical prostatectomy for prostate cancer. In 75 subjects with cancer and 51 with BPH the serum samples were analyzed for testosterone, dihydrotestosterone and SHBG. Significantly higher intraprostatic androgen concentrations, i.e. 8.85+/-6.77 versus 6.44+/-6.43 pmol/g, p<0.01 for dihydrotestosterone, and 4.61+/-7.02 versus 3.44+/-4.53 pmol/g, p<0.05 for testosterone, respectively, were found in patients with prostate cancer than in BPH. Higher levels in cancer tissue were found also for epitestosterone. However, no differences were found in serum levels. Highly significant correlations occurred between all pairs of intraprostatic androgens and also epitestosterone as well as between serum testosterone and dihydrotestosterone (p<0.001) in both BPH and cancer groups. Correlation was not found between corresponding tissue and serum testosterone and dihydrotestosterone, either in benign or cancer samples. The results point to importance of intraprostatic hormone levels for evaluation of androgen status of patients, contrasting to a low value of serum hormone measurement.     

IGFBP-4: A promising biomarker for lung cancer

Background: Insulin-like growth factor binding protein-4 (IGFBP-4), a member of the insulin-like growth factor (IGF) family, transports, and regulates the activity of IGFs. The pregnancy-associated plasma protein-A (PAPP-A) has proteolytic activity towards IGFBP-4, and both proteins have been associated with a variety of cancers, including lung cancer. Thus, we aimed to evaluate the use of IGFBP-4 and PAPP-A as potential biomarkers for lung cancer. Methods: Eighty-three volunteers, including 60 patients with lung cancer and 23 healthy individuals, were included in this study. The patients with lung cancer were selected based on their treatment status, histological subgroup, and stage of the disease. Enzyme-linked immunosorbent assays were used to assess the serum levels of IGFBP-4 and PAPPA, whereas the IGF-1 levels were measured using a chemiluminescent immunometric assay. Results: The serum IGFBP-4 levels in all patient groups, regardless of the treatment status and histological differences, were significantly higher than those in the control group (p<0.005). However, the serum PAPP-A levels in the untreated patient group were found to be higher than those in the control group, but this difference was not statistically significant (p=0.086). Conclusions: The serum PAPP-A and IGFBP-4 levels are elevated in lung cancer. However, IGFBP-4 may have better potential than PAPP-A as a lung cancer biomarker.     

Gonadectomy prevents endothelial dysfunction in fructose-fed male rats, a factor contributing to the development of hypertension

Insulin resistance has been shown to be associated with increased blood pressure (BP). The sex hormones estrogen and testosterone have opposing effects in the development of increased BP. Since testosterone has been implicated in increased BP following insulin resistance, we have tried to dissect out the effects of insulin resistance on endothelium-dependent vasorelaxation in the presence and absence of testosterone. Both gonadectomized and sham-operated male Wistar rats fed with a high-fructose diet developed insulin resistance, but BP increased only in the sham-operated rats. Reintroduction of testosterone in vivo restored the increase in BP, thereby abolishing the protective effects of gonadectomy. Fructose feeding did not affect plasma testosterone levels. Insulin resistance induced endothelial dysfunction in the mesenteric arteries of sham-operated rats, which was prevented by gonadectomy, thus suggesting a key role for testosterone in the pathogenesis of secondary vascular complications. Subsequent to blocking the actions of endothelium-dependent hyperpolarizing factor (EDHF), relaxation to acetylcholine (ACh) was lower in sham-operated fructose-fed rats compared with other groups, suggesting the involvement of nitric oxide (NO) in vasorelaxation. Inhibition of NO synthesis nearly abolished the ACh-evoked relaxation in both fructose-fed groups, thus suggesting a testosterone-independent impairment of EDHF-mediated relaxation. The improvement in endothelial function following gonadectomy could be ascribed to a NO component, although plasma nitrite and nitrate levels were unchanged. In summary, testosterone is essential in vivo for the development of endothelial dysfunction and hypertension secondary to insulin resistance, suggesting a facilitatory role for testosterone in increasing BP in fructose-fed male rats.     

Prostate cancer risk in testosterone-treated men

Men with classical androgen deficiency have reduced prostate volume and blood prostate-specific antigen (PSA) levels compared with their age peers. As it is plausible that androgen deficiency partially protects against prostate disease, and that restoring androgen exposure increases risk to that of eugonadal men of the same age, men using ART should have age-appropriate surveillance for prostate disease. This should comprise rectal examination and blood PSA measurement at regular intervals (determined by age and family history) according to the recommendations, permanently revisited, published by ISSAM, EAU, Endocrine Society….

Testosterone replacement therapy is now being prescribed more often for aging men, the same population in which prostate cancer incidence increases; it has been suggested that administration in men with unrecognised prostate cancer might promote the development of clinically significant disease. In hypogonadal men who were candidates for testosterone therapy, a 14% incidence of occult cancer was found. A percentage (15.2%) of prostate cancer has been found in the placebo group (with normal DRE and PSA) in the prostate cancer prevention study investigating the chemoprevention potential of finasteride.

The hypothesis that high levels of circulating androgens is a risk factor for prostate cancer is supported by the dramatic regression, after castration, of tumour symptoms in men with advanced prostate cancer. However these effects, seen at a very late stage of cancer development, may not be relevant to reflect the effects of variations within a physiological range at an earlier stage.

Data from all published prospective studies on circulating level of total and free testosterone do not support the hypothesis that high levels of circulating androgens are associated with an increased risk of prostate cancer. A study on a large prospective cohort of 10,049 men, contributes to the gathering evidence that the long standing “androgen hypothesis” of increasing risk with increasing androgen levels can be rejected, suggesting instead that high levels within the reference range of androgens, estrogens and adrenal androgens decrease aggressive prostate cancer risk. Indeed, high-grade prostate cancer has been associated with low plasma level of testosterone. Furthermore, pre-treatment total testosterone was an independent predictor of extraprostatic disease in patients with localized prostate cancer; as testosterone decreases, patients have an increased likelihood of non-organ confined disease and low serum testosterone levels are associated with positive surgical margins in radical retropubic prostatectomy.

A clinical implication of these results concerns androgen supplementation which has become easier to administer with the advent of transdermal preparations (patch or gel) that achieve physiological testosterone serum levels without supra physiological escape levels. During the clinical development of a new testosterone patch in more than 200 primary or secondary hypogonadal patients, no prostate cancer was diagnosed.     

A Low-Testosterone State Associated with Endometrioma Leads to the Apoptosis of Granulosa Cells

Although endometriosis is suspected to be a cause of premature ovarian insufficiency (POI), the mechanism(s) underlying this process have not been elucidated. Recently, androgens were shown to promote oocyte maturation and to play a role in folliculogenesis. In addition, several reports have documented low testosterone levels in the follicular fluid obtained from endometriosis patients. We therefore examined whether the low levels of serum testosterone are associated with the apoptosis of granulosa cells in follicles obtained from endometriosis patients. Serum samples were collected from 46 patients with endometriosis and from 62 patients without endometriosis who received assisted reproductive therapy. Specimens of the ovaries obtained from 10 patients with endometrioma were collected using laparoscopy. The mean serum testosterone concentration in the patients with endometriosis was significantly lower than that observed in the patients without endometriosis. Furthermore, high expression of a pro-apoptotic Bcl-2 member, BimEL, in the follicles was found to be associated with a low serum testosterone level. We clarified the underlying mechanisms using a basic approach employing human immortalized granulosa cells derived from a primary human granulosa cell tumor, the COV434 cell line. The in vitro examination demonstrated that testosterone inhibited apoptosis induced by sex steroids depletion via the PI3K/Akt-FoxO3a pathway in the COV434 cells. In conclusion, we elucidated the mechanism underlying the anti-apoptotic effects of testosterone on granulosa cells, and found that a low-testosterone status is a potentially important step in the development of premature ovarian insufficiency in patients with endometriosis.     

Intratumour amount of sex steroids in elderly breast cancer patients. An approach to the biological characterization of mammary tumours in the elderly

Interest in breast cancer in elderly women is growing as a result of the high frequency of cancer in older age groups. We measured tumour concentrations and circulating levels of testosterone, dihydrotestosterone (DHT) and oestradiol in 50 postmenopausal patients: 26 younger than 70 yr (median, 61.5, range 50–69) and 24 older than 70 yr (median, 74.5, range 70–82). Hormones were measured by radioimmunoassay (RIA) after extraction and separation on celite column chromatography. Intratumour levels of the three steroids were lower in the older than in the younger patients, but the difference was statistically significant only for DHT (P = 0.0126). The decrease in the tumour concentrations of testosterone and DHT in the older group was associated with a slight increase in circulating levels, yielding as final result a statistically significant decrease of the tissue/plasma (T/P) ratio of these hormones. No significant difference was observed between groups for oestradiol levels. The blood levels of testosterone, DHT and oestradiol were significantly correlated in the older group, but not in the younger group. In contrast, the tumour amounts of testosterone and DHT were found to be significantly associated only in the < 70 yr group. We concluded that the hormonal environment in which breast cancer develops is different in younger and older postmenopausal patients, and that the difference mainly concerns the intratumour amounts of androgens, suggesting that the steroids concur in the growth regulation of mammary tumours.     

The Value of Serum Prealbumin in the Diagnosis and Therapeutic Response of Tuberculosis: A Retrospective Study

Objective

The aim of this study was to examine serum prealbumin (PA) levels in patients with tuberculosis and lung cancer, and to evaluate the correlations of serum PA levels with clinicopathological characteristics.

Method

Total 760 patients were included in the study: 320 patients with tuberculosis, 320 patients with lung cancer, and 120 healthy subjects. Serum PA was detected using a biochemical analyzer to determine the value of serum PA in the diagnosis and therapeutic response of tuberculosis.

Results

Compared to lung cancer and healthy individuals, TB patients were more frequent in suffering from low serum PA (75.0% vs.30.9% vs.6.7%,P<0.01), and the serum PA levels of TB patients were significantly reduced (137.5±42.4 mg/L vs. 183.5±49.1 mg/L vs. 240.0±43.9 mg/L, P<0.01). Among various clinical characteristics, type (with pleuritis), age (≥60), ESR (>20 mm/h) and smoking status (≥20 pack×years) were associated with low serum PA levels of TB patients, while ECOG performance status (≥2) was associated with low serum PA levels of lung cancer patients. The change of serum PA levels was in accordance with the therapeutic effects of anti-TB drugs, which might present a valuable and objective indicator for monitoring the therapeutic effects of TB drugs on TB patients.

Conclusion

Low serum prealbumin levels are very common in TB patients and can be served as a potential indicator for differential diagnosis of lung cancer and monitoring the therapeutic effects of TB drugs.     

Gonadal function in male mountain bikers

Some studies reported testicular disorders associated with biking in mountain cyclists, which include injuries, erectile dysfunction, and higher scrotal temperatures. But none of these studies evaluated gonadal function. Therefore, the aim of this study was to evaluate gonadal function in male mountain bikers. Twenty-two male professional mountain bikers and 30 healthy noncyclist controls were included in the study. The mean age and body mass index were similar in both groups. Fasting blood samples for the measurement of the levels of total testosterone (TT), sex-hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were obtained from all study participants before any physical activity. In addition, because insulin sensitivity and leptin modulate gonadal function, the concentrations of insulin, glucose, and leptin were also measured in the same samples. Calculated free testosterone (cFT) and bioavailable testosterone (bioT) were calculated from SHBG and TT. Basal hormonal levels including insulin, leptin, LH, FSH, SHBG, TT, glucose, and homeostasis model assessment scores were similar between the groups. However, bioT and cFT levels were significantly lower (p ≤ 0.05) in the mountain bikers than those in the controls. Despite the lower mean testosterone levels in the study group, the levels of LH and FSH were similar to controls. Insulin and leptin do not contribute to lower testosterone levels. In conclusion, male mountain bikers have lower testosterone concentrations compared to controls. This alteration cannot solely be explained by testicular dysfunction. The etiology of lower testosterone levels in cyclists appears to be complex and requires further research. The influence of such a decline on the athlete's performance, quality of life, and muscle strength is not known as yet.     

Beta-CTX and ICTP act as indicators of skeletal metastasis status in male patients with non-small cell lung cancer

Bone metastasis is common in lung cancer patients and associated with reduced quality of life and reduced overall and median survival, so the early detection of bone metastasis and monitoring of its status is very important for clinicians. Serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), beta isomer of C-terminal telopeptide of type I collagen (beta-CTX) and cross-linked C-terminal telopeptide of type I collagen (ICTP) were compared with regard to their usefulness as indicators of bone metastasis in lung cancer. The serum concentrations of the 4 markers were measured by commercially available tests in 96 male patients with non-small cell lung cancer and 30 male patients with other pulmonary diseases. The levels of both a-CTX and ICTP were significantly higher in 61 lung cancer patients with bone metastases than in 35 lung cancer patients without bone metastases (both p<0.001), and significantly correlated with the extent of bone disease. Although ICTP had a better sensitivity and accuracy than beta-CTX (75.4% vs 65.6% and 72.9% vs 68.8%, respectively), they had a similar area under the receiver operating characteristic curve (0.85 vs 0.83). These results support the use of beta-CTX and ICTP as an adjunct tool for the diagnosis and screening of bone metastasis in lung cancer.     

Transverse testicular ectopia with abnormal karyotype - a case report

OBJECTIVES: Growth disturbances and developmental malformations of external genitalia, such as hypospadias, bifid scrotum and micropenis, coexisting with non-palpable testes, may develop as a result of primary endocrinological dysfunctions as well as an effect secondary to chromosomal aberrations. Therefore, patients with these symptoms require specific diagnostic and therapeutic approaches. Design and methods: We present an example of TTE as a presentation of karyotype abnormalities. Clinical presentation - 9.5 year old boy presented with hypospadias, bilateral cryptorchidism and right inguinal hernia and short stature. Results: Endocrine test showed low testosterone levels with adequate gonadal response. Laparoscopy was performed and revealed the presence of TTE. Conclusions: The presence of mosaic karyotype with abnormal Y chromosome does not exclude a possibility of testis migration disorders, including TTE, caused by other (possibly genetic) factors. Laparoscopy is a technique of choice for diagnosis and treatment in cases of cryptorchidism.     

Effects of egg yolk testosterone on growth and immunity in a precocial bird

In oviparous vertebrates, maternal steroid allocation to eggs can have important fitness consequences for the offspring. However, elevated testosterone levels are not only associated with beneficial postnatal effects, such as enhanced growth and high social status, but may also entail costs by suppressing the immune system. In this study, testosterone levels in eggs of Chinese painted quail (Coturnix chinensis) were experimentally manipulated to evaluate its effects on growth and immunocompetence. Testosterone did not affect embryonic development, body size or growth during the first 20 days. However, elevated testosterone levels during embryonic development were immunosuppressive for chicks with inherently higher growth rate. Adaptive scenarios where only beneficial effects of increased testosterone levels are considered may therefore need to be re-evaluated.     

Serum of patients with prostatic cancer or benign prostatic hypertrophy contains nonpolar testosterone.

We have previously described a nonpolar form of radioimmunoassayable serum testosterone (NPT) not measured by available antitestosterone antibodies. It is detected by mild alkaline hydrolysis of the petroleum ether extract of serum and subsequent radioimmunoassay. The properties of NPT are consistent with that of a fatty acid ester of testosterone or dihydrotestosterone. The serum of young males contains 1 to 3 ng/ml NPT, but it is not detected in female serum. We measured serum testosterone and NPT levels in 36 men between 58 and 87 years of age. Seventeen subjects with advanced prostatic cancer (NPT 1.70 +/- 1.44 ng/ml) were compared with a control group consisting of six patients with benign prostatic hypertrophy (BPH) and 13 patients with no prostatic disease (NPT 0.72 +/- 0.46, P = 0.017). There was no significant difference between BPH patients and patients with no prostatic disease; the results were pooled. The concentration of NPT in prostatic cancer patients but not in controls was inversely correlated with that of testosterone. Immunoassayable testosterone was present in the serum of two orchiectomized patients and, therefore, cannot derive solely from the testes.     

Chronobiological concepts underlying the chronotherapy of human lung cancer

This article reviews the experimental and clinical data that form the basis for the chronotherapy of lung carcinoma, specifically, nonsmall cell lung cancer (NSCLC). Circadian rhythms in cell kinetics, immunological and endocrinological endpoints, and tumor markers are reviewed. Chronopharmacology and chronotolerance studies on laboratory animals and clinical observations on cancer patients involving the main drugs active in lung carcinoma have prompted prospective Phase I-III studies to evaluate the application of chronobiologic concepts in the treatment of NSCLC. Circadian rhythmicity in host tolerance (chronotolerance) to medications has been confirmed in two prospective randomized lung cancer trials; a large phase II study has established the value of chronobiologic concepts to improve the therapeutic index of advanced NSCLC.     

Chronobiological concepts underlying the chronotherapy of human lung cancer

This article reviews the experimental and clinical data that form the basis for the chronotherapy of lung carcinoma, specifically, nonsmall cell lung cancer (NSCLC). Circadian rhythms in cell kinetics, immunological and endocrinological endpoints, and tumor markers are reviewed. Chronopharmacology and chronotolerance studies on laboratory animals and clinical observations on cancer patients involving the main drugs active in lung carcinoma have prompted prospective Phase I–III studies to evaluate the application of chronobiologic concepts in the treatment of NSCLC. Circadian rhythmicity in host tolerance (chronotolerance) to medications has been confirmed in two prospective randomized lung cancer trials; a large phase II study has established the value of chronobiologic concepts to improve the therapeutic index of advanced NSCLC.     

Invasive Breast Cancer After Initiation of Testosterone Replacement Therapy in A Man—A Warning To Endocrinologists

ObjectiveTo alert fellow endocrinologists of a rare side effect of testosterone therapy, for which men with hypogonadism must receive appropriate counseling and monitoring.MethodsWe present clinical features, laboratory data, and histopathologic findings in a man with hypogonadism who received testosterone replacement therapy.ResultsA 61-year-old man was referred to an endocrinologist after presenting to his general practitioner with erectile dysfunction and low libido. He had no history of hypothalamic, pituitary, or testicular disorders. There were no other illnesses or medications to account for low testosterone levels. Physical examination was unremarkable. There was no family history of malignant disease. Biochemical investigations confirmed the presence of primary hypogonadism, for which no cause (including Klinefelter syndrome) was identified. Testosterone therapy was initiated to improve sexual function and preserve bone density. Five weeks later, the patient returned to his general practitioner, complaining of a gradually enlarging lump in his right breast. When biopsy showed breast cancer, testosterone therapy was discontinued. Right mastectomy and axillary node clearance were performed. Further histologic examination revealed estrogen receptor-positive, invasive carcinoma, without nodal involvement. The patient remains on tamoxifen therapy and is undergoing follow-up in the breast clinic. After 6 months of treatment, estradiol levels were undetectable, and testosterone levels remained low.ConclusionAlthough breast cancer has been described in men with hypogonadism receiving long-term testosterone replacement therapy, to our knowledge this is the first report of breast cancer becoming clinically manifest after a short duration (5 weeks) of testosterone treatment. This case should remind clinicians that men receiving testosterone therapy should be warned of the risk of not only prostate cancer but also breast cancer. Patient self-monitoring and breast examinations by the attending physician are recommended. (Endocr Pract. 2008;14: 201-203)     

Aryl hydrocarbon hydroxylase activity in pulmonary alveolar macrophages and lymphocytes from lung cancer and noncancer patients: A correlation with family histories of cancer

Aryl hydrocarbon hydroxylase (AHH) activity was measured in pulmonary alveolar macrophages (PAMs) and peripheral blood lymphocytes from cigarette smokers with and without primary lung cancer. Frequency distribution analysis of AHH induction ratios for the two groups revealed an increased number of individuals in the lung cancer patient group with high lymphocyte induction values (P less than 0.05). A similar increase was not shown for high-PAM AHH values in lung cancer patients (P greater than 0.2). When individual PAM and lymphocyte AHH values were compared between noncancer and lung cancer patients, a positive correlation was observed for noncancer patients (r=0.195, P less than 0.001), but no correlation of these values was noted for lung cancer patients. The lung cancer patients were divided into three subgroups of patients showing (I) high PAM and low lymphocyte AHH levels, (II) low PAM and low lymphocyte AHH levels, and (III) low PAM and high lymphocyte AHH levels. When the incidence of family history of cancer was compared for these subgroups, no family cancer history was recorded for persons in subgroup II; however, individuals in subgroups I and III presented family cancer history incidence of 9.5% and 39.3%, respectively. Patients in group III averaged 6 years younger than those in group I. These data suggest that familial factors may be identified among lung cancer patients and that these factors appear to associate as either a cause of an effect with the capacity of pulmonary alveolar macrophages and lymphocytes to be induced for AHH. The data support the hypothesis that high AHH values may be characteristic of lung cancer patients but show that enzyme values determined from a single tissue, either PAMs or lymphocytes, may not be appropriate for showing whether high AHH inducibility is correlated with lung cancer.     

Second to fourth digit ratio, testosterone and perceived male dominance

Previous studies have shown that male faces with extreme features associated with testosterone are perceived as dominant and masculine. Women have been reported to prefer more masculinized male faces as they may consider testosterone markers to be an 'honest' indication of good health, and such considerations may underlie their aesthetic preferences. However, pronounced testosterone facial markers are also associated with dominance, and several negative personality traits. This suggests that female aesthetic preferences may be an adaptive compromise between positive attributes associated with higher than average testosterone, and negative attributes associated with more extreme masculinization. This current study attempts to clarify the role of hormone markers in female perceptions of dominance, masculinity and attractiveness, in male facial images. Recent evidence suggests that the relative length of the 2nd to 4th finger (2D : 4D ratio) is a pointer to prenatal testosterone levels and may thus serve as a window to the prenatal hormonal environment. We measured 2D : 4D in a sample of male college students and took salivary samples to analyse circulating levels of testosterone. Women rated facial images of these males for dominance, masculinity and attractiveness. Our results show that male 2D : 4D was significantly negatively related to perceived dominance and masculinity but not attractiveness. Circulating testosterone levels were not related to dominance, masculinity or attractiveness. These findings suggest that: (i) high prenatal levels of testosterone serve to 'organize' male facial features to subsequently reflect dominance and masculine characteristics presumably activated during puberty; and (ii) attractiveness is not directly related to testosterone levels. We conclude that facial dominance and masculinity reflect a male's perceived status rather than his physical attraction to women.     

吉非替尼联合GP化疗方案治疗晚期非小细胞肺癌的效果及对血清CEA、SCC、NSE、CYFRA21-1水平的影响

目的:研究吉非替尼联合吉西他滨和顺铂(GP)化疗方案治疗晚期非小细胞肺癌的效果及对血清癌胚抗原(Carcinoembbryonic antigen,CEA)、鳞状细胞癌相关抗原(Squamous cell carcinoma,SCC)、神经元特异烯醇化酶(Neuron-specific enolase,NSE)、细胞角蛋白19片段(Cytokeratin-19-fragment,CYFRA21-1)水平的影响。方法:选取2016年6月～2018年6月我院收治的晚期非小细胞肺癌患者110例,采用随机数字表法将患者分为两组,每组55例。对照组患者给予GP化疗方案,观察组在对照组的基础上给予吉非替尼。比较两组患者的临床治疗效果,治疗前后血清肿瘤标志物水平和生活质量的变化以及不良反应发生情况。结果:治疗后,观察组疾病控制率为86.67%,对照组为74.55%,观察组显著高于对照组(P0.05);两组治疗后血清CEA、SCC、NSE和CYFRA21-1水平均较治疗前显著下降,且观察组以上指标均显著低于对照(P0.05);两组治疗后FACT-L各项评分包括躯体状况、社会家庭状况、情感状况、肺癌特异性模块和功能状况评分均较治疗前显著升高,且观察组以上指标均显著高于对照(P0.05)。治疗期间,观察组患者白细胞减少、血小板减少、肝肾功能异常的发生率显著低于对照组(P0.05),两组贫血、恶心呕吐的发生率比较无统计学差异(P0.05)。结论:与GP化疗方案相比,吉非替尼联合GP化疗方案可更显著提高晚期非小细胞肺癌患者的治疗效果,改善其生活质量,且安全性较高,可能与其降低血清CEA、SCC、NSE和CYFRA21-1水平有关。