Immune complexes and acute phase proteins in human cancer: preliminary evaluation by laser nephelometric techniques

The serum levels of circulating immune complexes (IC) were evaluated by a new 'direct' laser nephelometric assay, concomitantly with four acute phase proteins (APP), in 167 patients with various neoplasms at different stages. The present study confirms the presence of IC in the sera of cancer patients and, in the breast cancer group, there is a significant correlation with the progression of the disease. Among the APP, in several cancer groups, C-reactive protein, haptoglobin and alpha 1-acid glycoprotein are more elevated than in controls, and a trend to display higher values is observed in the subjects with metastatic disease; particularly, the frequency of patients with 3 or more proteins above the normal levels is significantly higher in metastatic than in localized cancers (p less than 0.09).     

Relationship Between the SER Treatment Period and Prognosis of Patients with Small Cell Lung Cancer

Purpose: To explore the relationship between SER (time between the start of any treatment and the end of radiation therapy) and the survival of patients with limited-stage small cell lung cancer. Materials and Methods: Between 2008 and 2013, 135 cases of limited-stage small cell lung cancer (LS-SCLC) treated with consecutively curative chemoradiotherapy were included in this retrospective analysis. In terms of SER, patients were divided into early radiotherapy group (SER<30 days, n=76) and late radiotherapy group (SER≥30 days, n=59) with a cutoff of SER 30 days. Outcomes of the two groups were compared for overall survival. Results: For all analyzable patients, median follow-up time was 23.8 months and median overall survival time was 16.8 months. Although there was no significant differences in distant metastasis free survival between the two groups, patients in early radiotherapy group had a significantly better PFS (p=0.003) and OS (p=0.000). Conclusions: A short SER may be a good prognostic factor for LD-SCLC patients treated with concurrent chemoradiotherapy.     

Life-prolonging effect of immunocell BAK (BRM activated killer) therapy--evidence based integrative medicine

We devised an innovative type of immunocell therapy called biological response modifier (BRM)-activated killer (BAK) therapy, which utilizes most of non-MHC (major histocompatibility complex)-restricted lymphocytes, CD56-positive cells including gammadelta T cells and NK cells. CD56-positive cells are neuro-immune-endocrine (NIE) multifunctional, integrated cells. We enrolled 30 immunosuppressed patients whose immunosuppressive acidic protein (IAP) levels in serum were over 580 microg/ml, and 63 immunoreactive solid cancer outpatients whose IAP level in serum were under 580 microg/ml. Treated with BAK therapy, the mean survival time of immunosuppressed patients was 5.0 months. On the other hand, survival time of immunoreactive advanced postoperative patients (stage IV) and inoperable lung cancer patients (stage IIIb) was 27.1 months. BAK therapy has a life-prolonging effect without any adverse effects and maintains satisfactory quality of life (QOL) for advanced solid cancer patients. Based on this evidence, we propose what can be called Integrative medicine which is neither Western nor Chinese medicine.     

Effect of mithramycin therapy on strontium and calcium metabolism in cancer patients (a preliminary report)

The short-term effects of acute mithramycin therapy on calcium homeostasis and strontium-85 kinetics were studied in four patients with metastatic cancer. Fecal calcium content increased after therapy while urinary calcium excretion decreased, but there was no net change in total calcium excretion. Mithramycin lowered the serum calcium level in three patients with either obvious osseous metastasis or hypercalcemia, but no change was observed in a fourth patient without osseous pathology and normal serum levels. The strontium-85 (Sr⁸⁵) kinetic data revealed an increase in the skeletal clearance (“accretion”) in three patients and no change in the fourth. There was no change in the extrinsic (excretory) clearance rate in any patient. These data suggest that acute mithramycin therapy lowered serum calcium by promoting non-excretory removal from blood (internal skeletal clearance) rather than by increasing calcium excretion.     

Evaluation of a tumor-associated antigen CA 15-3 in the sera of patients with breast cancer

Serum levels of CA 15-3 were determined in normal women and patients with breast cancer and other diseases. The serum concentration of normal subjects was 9.8 +/- 4.4 units/ml (mean +/- S.D., n = 97). The patients with primary and recurrent breast cancer had significantly higher levels of CA 15-3, their values being 23.1 +/- 59.6 (n = 47) and 127.6 +/- 179.7 (n = 32) units/ml, respectively. When the value of 20 units/ml was used as the cutoff for the normal value, the positive rates were 4%, 26% and 75% in normal women and breast cancer patients primary and recurrent, respectively. No increased levels were found in the sera of patients with benign breast diseases or with gastrointestinal, thyroid, lung and other cancers. The elevated levels of CA 15-3 decreased after successful therapy both in primary and recurrent breast cancer patients, while there was no change in nonresponders. The measurement of serum CA 15-3 would be useful for monitoring the therapy and for detection of the recurrence of breast cancer.     

Stability of decisional role preference over the course of cancer therapy

Cancer patients vary in their preferred level of involvement in medical decision making, and responding to patients' desired level of involvement is a key element of good medical care. While the literature has clearly demonstrated heterogeneity among cancer patients' preferences, less is known about how the preferences of any given patient may change over time. This longitudinal study compared cancer patients' preferences for involvement in medical decision making from the time of diagnosis to the time of completion of therapy. Data from 729 cancer patients with mixed diagnoses were analyzed. Most patients reported a change in preferred level of involvement over time, and multivariate analysis demonstrated that patients tend to prefer a decreasing level of involvement over time (p<0.0001). Stability of patients' preferences was also associated with type of cancer, but not with other sociodemographic characteristics. The results from this study highlight the importance of reevaluating patients' preferences for involvement in medical decision making throughout the course of cancer therapy, as such preferences are likely to change.     

Health-related quality of life in men after treatment of localized prostate cancer with external beam radiotherapy combined with (192)ir brachytherapy: a prospective study of 93 cases using the EORTC questionnaires QLQ-C30 and QLQ-PR25

PURPOSE: To describe prospectively the long-term health-related quality of life (HRQOL) and treatment-related symptoms in patients with localized prostate cancer treated with neoadjuvant androgen deprivation therapy and radical radiotherapy (RT), including external beam RT and iridium high-dose-rate brachytherapy, and to compare them with age-matched normative data. METHODS AND MATERIALS: A total of 93 patients with T1-T3a tumors consecutively treated with definitive RT at our institution completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and QLQ-prostate specific 25-item (PR25) module twice at an 18-month interval 0-18 months after RT. Subgroups were analyzed regarding acute and late effects on symptoms and quality of life. RESULTS: The main analysis included 80 patients who were disease free at the final assessment. The levels of HRQOL were generally high, did not change over time, and were comparable to the normative data. Symptom development (urinary, bowel, and sexual) correlated well with the known acute and late effects of radical RT and neoadjuvant androgen deprivation therapy. CONCLUSION: Combining external beam RT and HDR brachytherapy when treating prostate cancer did not appear to impair HRQOL and was comparable to that of other brachytherapy methods. The negative contribution from late neoadjuvant androgen deprivation therapy on symptom development seemed to be substantial but mostly transitory. Additional research is needed to determine the long-term HRQOL (3-5 years), and interventional randomized studies are suggested.     

肺癌化疗（VCR＋铂类）的急性期蛋白水平的变化

作者观察了２２例肺癌患者用ＶＣＲ＋ＤＤＰ或ＣＢＤＣＡ化疗前及化疗第３天和第５天血清ａ１－抗胰蛋白（ＡＡＴ）、触珠蛋白（ＨＰ）和转铁蛋白（Ｔｆ）等三项急性期蛋白的水平。结果表明，肺癌患者化疗前血清ＡＡＴ和Ｈｐ显著高于正常值（ｐ值分别小于０．０１和０．０５），血清Ｔｆ显著低于正常值（Ｐ＜０．０１）。化疗第３天和第５天时，化疗有效的９例患者其血清ＡＡＴ较化疗前显著升高（Ｐ＜０．０５），无效的１３例患者其血清ＡＡＴ尤明显变化。血清ＨＰ和Ｔｆ在化疗过程中无显著变化。化疗过程中血清ＡＡＴ浓度的升高率与化疗近期效果有关。结果提示，肺癌化疗过程中肿瘤组织的坏死可导致明显的急性期反应，且通过观察化疗初期血清ＡＡＴ升高率可估计肺癌对化疗的敏感性。     

前列腺癌骨转移患者89SrCl2治疗后血清E-选择素浓度的变化

目的:观察前列腺癌骨转移患者89SrCl2治疗后血清E-选择素浓度的变化,了解核素治疗是否减少参与肿瘤细胞转移过程的细胞粘附分子-内皮细胞选择素(E-选择素)的表达.方法:23例经99Tcm-MDP骨扫描证实存在多发性骨转移的雄激素非依赖性前列腺癌患者,进行89SrCl2治疗,于治疗时、治疗后2、4、6、8个月测定患者血清E-选择素浓度,其中8例于初次治疗后8个月时接受第二次治疗.同时测定患者血清前列腺特异抗原(PSA),10例健康体检者作为对照.结果:前列腺癌多发性骨转移患者的血清E-选择素浓度在89SrCl2治疗后明显降低,治疗前后的血清E-选择素和PSA浓度之间不存在明显相关性.结论:89SrCl2可以抑制E-选择素的表达,这种作用可能为放射性核素抑制恶性肿瘤骨转移的机制之一.     

Study of dyadic communication in couples managing prostate cancer: a longitudinal perspective

Objective: Cancer patients and partners often report inadequate communication about illness‐related issues, although it is essential for mutual support and informal caregiving. This study examined the patterns of change in dyadic communication between patients with prostate cancer and their partners, and also determined if certain factors affected their communication over time. Method: Using multilevel modeling, this study analyzed longitudinal data obtained from a randomized clinical trial with prostate cancer patients and their partners, to examine their communication over time. Patients and partners (N=134 pairs) from the usual‐care control group independently completed baseline demographic assessment and measures of social support, uncertainty, symptom distress, and dyadic communication at baseline, and 4‐, 8‐, and 12‐month follow‐ups. Results: The results indicated that (1) patients and partners reported similar levels of open communication at the time of diagnosis. Communication reported by patients and partners decreased over time in a similar trend, regardless of phase of illness; (2) phase of illness affected couples' open communication at diagnosis but not patterns of change over time; and (3) couples' perceived communication increased as they reported more social support, less uncertainty, and fewer hormonal symptoms in patients. Couples' demographic factors and general symptoms, and patients' prostate cancer‐specific symptoms did not affect their levels of open communication. Conclusions: Perceived open communication between prostate cancer patients and partners over time is affected by certain baseline and time‐varying psychosocial and cancer‐related factors. The results provide empirical evidence that may guide the development of strategies to facilitate couples' interaction and mutual support during survivorship. Copyright © 2010 John Wiley & Sons, Ltd.     

Calcitonin concentrations in lung cancer and non-malignant pulmonary diseases

The serum immunoreactive calcitonin (ICT) concentration was estimated in 107 patients with lung cancer of various cell types, 46 normal subjects and 24 non-cancer patients with various pulmonary diseases. Eighty-one of the cancer patients had localized lung cancer and the rest 26 primary lung cancer with metastases to other organs. The ICT was found significantly increased in the lung cancer patients. The highest ICT values were found in patients with lung cancer and metastases to other organs, especially to the liver. In localized disease, patients with small-cell carcinoma of the lung showed the highest, while those with adenocarcinoma and squamous-cell type demonstrated the lowest ICT concentrations. In 46 patients with lung cancer, serial determinations of serum ICT levels showed significantly decreased calcitonin levels in the patients who responded well to therapy with cytostatics, X-rays or both after more than 2 months of therapy. Fluctuations of ICT levels were in agreement with the regression or progression of the disease.     

Benefits of medroxyprogesterone acetate (MPA) in advanced or recurrent breast cancer with higher serum concentration

The efficacy of medroxyprogesterone acetate (MPA) therapy in controlling progressive measurable metastatic breast cancer was assessed in 61 patients. In addition serum MPA concentrations were measured by high performance liquid chromatography (HPLC) and subjective effects of treatment were monitored. Overall 24 patients (39.3%) achieved an objective response(2 complete responses [ CR ] and 22 partial responses [ PR ]). There was no significant relationships between response to therapy and menopausal status, metastatic sites, previous therapy, histological type, or disease-free interval. Patients with estrogen (ER) and progesterone (PgR) receptor-positive tumors responded more frequently. Significant differences in serum MPA concentrations were seen between responders and non-responders, objective tumor shrinkage being seen in patients with serum levels in excess of 55 ng/ml. There were few cases responding to the therapy with serum MPA concentrations lower than 25 ng/ml. The serum MPA levels significantly correlated with an improvement in the performance status and survival. Patients with serum MPA concentrations lower than 25 ng/ml had significantly poorer survival. There was a significant relationship between MPA level and dose per area of boby surface (mg/ m(2)) in cases with CR or PR or no change (NC). However, the serum levels of patients with progressive disease despite therapy were lower than the expected levels based on the body surface area. This study demonstrated that serum MPA concentration is a determining factor for therapeutic benefit in advanced or recurrent breast cancer.     

Oral high-dose medroxyprogesterone acetate (MPA) treatment: cortisol/MPA serum profiles in relation to breast cancer regression

Medroxyprogesterone acetate (MPA), a potent synthetic progestin, has been widely used in the hormonal treatment of advanced breast cancer, but presently with varying dose schedules. The availability of a sensitive RIA-method for determination of serum MPA has stimulated the research on MPA serum levels in patients after repeated MPA administration. The aim of this study was to assay blood level profiles of MPA as well as of cortisol during repeated high-dose orally administered MPA. 34 patients with metastatic breast cancer were enrolled in this study. 12 patients died already within the first 4 weeks of MPA treatment due to multiple metastases. The dosage regimen based on the daily oral administration of 1,000 mg MPA suspension. During MPA treatment, a decrease of cortisol serum levels was observed in nearly all patients. Within the observation time of 8 months out of 22 evaluable cases 18.2% responded to the therapy (complete and partial response). No change was observed in 36.4% and progression in 45.5% of the patients. Within the remission (complete and partial) group, a good correlation between constant MPA serum levels above 150 ng/ml and remission was observed. But in the groups with no change and progression no such correlation could be observed.     

Serum lactic dehydrogenase and isoenzyme changes in clinical cancer

Total LDH and LDH isoenzyme values were measured in serum collected from patients at the time of hospital admission. Changes in isoenzyme values were not necessarily found to depend upon elevated total serum LDH levels. Many patients with normal levels of serum LDH had abnormal isoenzyme patterns usually related to a disease process. A large percentage of patients with neoplastic disease had statistically increased LDH 5 values. Many other patients with either acute and/or chronic disease failed to reflect changes in the isoenzyme values.     

High levels of serum HER-2/neu and YKL-40 independently reflect aggressiveness of metastatic breast cancer.

PURPOSE: To evaluate serum levels of HER2 (an epithelial growth factor) and YKL-40 (a growth factor participating in inflammation and remodeling of the extracellular matrix) in relation to outcome in patients with their first diagnosis of recurrent breast cancer. DESIGN: Serum HER2 and YKL-40 levels were measured in 100 patients referred with their first metastatic manifestation of breast cancer before first line anthracycline-based therapy and related to response to therapy, metastatic pattern, time to progression, and overall survival. During the observation period of 64-84 months, 89 patients died of breast cancer. RESULTS: The patients had higher serum HER2 and YKL-40 levels than healthy females (P < 0.0001). Serum HER2 was elevated in 32% of the patients and serum YKL-40 in 30%. These patients were more sick (P < 0.01) and more often had parenchymal involvement (P < 0.0005), especially liver metastases (P < 0.00005). In multivariate Cox analysis, high serum levels of HER2 or YKL-40 or lack of estrogen receptors independently doubled the relative risk of progression and dying (P < 0.001) even after accounting for other independent prognostic variables, such as axillary nodal involvement at primary diagnosis, liver metastases, and more than two metastatic sites. Fewer patients with high serum HER2 or YKL-40 or lack of estrogen receptors responded with a complete remission on chemotherapy (P = 0.005, 0.036, and 0.006). In these patients, high serum YKL-40 was a stronger predictor of survival than high serum HER2 or lack of estrogen receptors. CONCLUSIONS: High serum HER2 and YKL-40 independently identified subgroups of patients with metastatic breast cancer with a poor prognosis.     

胃癌患者治疗前后血清可溶性肿瘤坏死因子受体Ⅰ的变化及其意义

目的探讨胃癌患者治疗前后血清可溶性坏死因于受体（ｓＴＮＦ－Ⅰ）水平的临床意义。方法应用酶联免疫吸附测定（ＥＬＩＳＡ）的方法测定了３４例胃癌患者ｓＴＮＦＲ－Ⅰ水平。结果胃癌患者血清ｓＴＮＦＲ－Ⅰ水平明显高于正常人（Ｐ＜０．０１），且与临床分期有关，病情越晚，ｓＴＮＦＲ－Ⅰ水平越高，ｓＴＮＦＲ－Ⅰ水平超过３．００ｎｇ／ｍｌ者预后不良；治疗有效者ｓＴＮＦＲ－Ⅰ均显著下降（Ｐ＜０．０１），２４例治疗后４～８个月再次采血检验，８例无瘤生存者ｓＴＮＦＲ－Ⅰ水平降至正常，其余１６例肿瘤未控制或复发转移者血清ｓＴＮＦＲ－Ⅰ水平升高。结论血清ｓＴＮＦＲ－Ⅰ测定对胃癌疗效观察、病情监测及预后判断有重要意义。     

Serum thyroid hormone changes during whole body hyperthermia

In order to elucidate changes in thyroid hormone metabolism during acute heat stress, we measured sequentially serum thyroxine (T4), triiothyronine (T3), and reverse T3 (rT3) levels in 5 patients with neoplasia during treatment with whole body hyperthermia. The core temperature was raised from 37.0 degrees C to 42.0 degrees C over a 2-hour period, maintained at 42.0 degrees C for 2 hours, and then cooled to 37.0 degrees C over 2 hours. This short period of severe hyperthermia produced a fivefold rise in rT3 and a fall in T3 levels to one half of baseline levels. T4 and free T4 levels increased slightly, but thyrotropin (measured in two patients) did not change. These changes in T3 and rT3 levels were detectable at the fourth hour after onset of hyperthermia, were maximal at 24 and 48 hours, and in one patient were uncorrected after 4 days. We conclude that this reciprocal change in T3 and rT3 levels is a response to stress and may represent in part adaptation to a high environmental temperature by the suppression of theromengic T3. Whole body hyperthermia of short duration for cancer therapy produces profound changes in the peripheral degradation of thyroxine, which last for several days. This must be considered in the management of patients receiving hyperthermia, and the technique itself may prove to be a useful model for the study of adaptation to heat stress.     

Serum posaconazole levels during acute myeloid leukaemia induction therapy: correlations with breakthrough invasive fungal infections

The usefulness of posaconazole therapeutic drug monitoring (TDM) is still a matter of debate. A correlation between posaconazole serum levels and breakthrough invasive fungal infections (IFI) has not been clearly demonstrated so far. We analysed posaconazole serum levels in patients with acute myeloid leukaemia (AML) during induction therapy and correlated them with the incidence of breakthrough IFI and the need of systemic antifungal therapy. Overall, 77 AML patients receiving posaconazole were evaluated for serum levels; breakthrough IFI were observed in five with at least one posaconazole TDM (6.5%). Median serum level was 534 ng ml^?1 (IQ range: 298.5–750.5 ng ml^?1) and did not change significantly over time. Four of the 40 patients with median posaconazole levels <500 ng ml^?1 developed IFI, as compared with only 1 of the 37 patients with median levels ≥500 (10% vs. 2.7%, P = 0.19). Median posaconazole levels on day 7 were 384.5 ng ml^?1 (IQ range: 207–659 ng ml^?1) and 560.5 ng ml^?1 (IQ range: 395–756 ng ml^?1) in patients requiring or not systemic antifungal treatment respectively (P = 0.067). These results seem to confirm that higher median serum levels of posaconazole correlate with higher prophylactic efficacy against proven/probable IFI and with lesser need of systemic antifungal therapy.     

Thymidine kinase in breast cancer

The enzyme thymidine kinase is associated with DNA synthesis. Thymidine kinase serum levels were studied in normal controls (n = 20), patients with primary breast cancer (n = 60), patients with systemic breast cancer (n = 20) and as a non-cancer disease control group in patients with inflammatory gastrointestinal disorders (n = 20). Comparison of pretreatment values in the cancer patients with the normal controls showed a significant difference between the three groups in relation to stage of disease: mean values 4.22 (+/- 1.08), 6.22 (+/- 2.24) and 9.79 (+/- 7.56) pmol ml-1 h-1 for normal controls, operable breast cancer and systemic breast cancer respectively (P less than 0.005; analysis of variance). Patients with systemic breast cancer had a significantly elevated serum thymidine kinase level compared to controls (P less than 0.01) and patients with primary operable cancer (P less than 0.05). Patients with primary operable cancer had significantly higher serum thymidine kinase levels over normal controls (P less than 0.01). Mean serum TK in patients with inflammatory gastrointestinal diseases was similar to normal controls but significantly less than both patients with primary operable breast cancer and patients with systemic breast cancer. Twenty patients with operable breast cancer were followed up after primary surgery by serial 3-monthly thymidine kinase levels in the disease free interval. Four patients have developed systemic recurrence with a rise in the mean thymidine kinase value to 14.3 pmol ml-1 h-1. Ten patients with advanced breast cancer had serial thymidine kinase levels measured 2-monthly during the first 6 months of primary hormone therapy. The serum values fell in all five responders (mean 9.12-4.78 pmol ml-1 h-1) and rose in all five progressors (mean 8.62-38.5 pmol ml-1 h-1). Serum thymidine kinase reflects stage of disease in breast cancer. Serial thymidine kinase levels in patients with systemic breast cancer reflected response to systemic therapy.     

Tamoxifen and aromatase inhibitors differentially affect vascular endothelial growth factor and endostatin levels in women with breast cancer.

PURPOSE: Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance. We explored the effects of tamoxifen and aromatase inhibitors on concentrations of VEGF and endostatin in plasma, serum, and platelet releasate (induced by platelet activation). EXPERIMENTAL DESIGN: VEGF and endostatin concentrations were measured with a quantitative immunoassay before and after 1 to 5 weeks of treatment in 30 women with breast cancer treated with either tamoxifen (n = 14) or aromatase inhibitors (n = 16). Platelet activation was induced by a thrombin receptor agonist. RESULTS: Tamoxifen therapy resulted in an increase in platelet releasate concentrations of VEGF (P = 0.01) but no change in plasma VEGF. In contrast, aromatase inhibitor therapy did not affect serum, plasma, or platelet releasate VEGF. In univariate analysis, aspirin use attenuated the tamoxifen-associated increase in VEGF in the platelet releasate and decreased serum levels of VEGF (P = 0.03). Aromatase inhibitor therapy resulted in a decrease in serum endostatin concentrations (P = 0.04), whereas plasma concentrations of endostatin tended to be higher during treatment with aromatase inhibitors (P = 0.06). Tamoxifen therapy resulted in no change in serum or plasma endostatin concentrations. Platelet releasate concentrations of endostatin did not change with either treatment. Interindividual variability was noted among both aromatase inhibitor--and tamoxifen-treated patients. CONCLUSIONS: Tamoxifen and aromatase inhibitor therapy affect VEGF and endostatin levels and likely contribute to the angiogenic balance in breast cancer patients. Aspirin decreased the proangiogenic effects of tamoxifen, suggesting that antiplatelet and/or antiangiogenic therapy might improve the effectiveness of tamoxifen in women with breast cancer.