[The Origin and Academic Characteristics of Xujiang School].

Xujiang School of acupuncture and moxibustion has a long history with distinctive academic characteristics and regional influence. Xujiang School, originated from Xi Hong in Song Dynasty, is the oldest acupuncture and moxibustion school recorded in Chinese history. Later, it was passed down from family to family for more than ten generations. The tenth generation Xi Xinqing passed it on to Chen Honggang and gradually evolved into a school of acupuncture and moxibustion with regional characteristics and a certain national influence. In terms of academic characteristics, doctors in Xujiang School kept innovating based on the Classics.Its acupuncture and moxibustion academic ideas including reinforcement and reduction , point selection and searching for the primary cause of disease in treatment have had an important impact on contemporary acupuncture in clinic.

[Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study].

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

[Clinical features and survival analysis in non-M(3) acute myeloid leukemia patients with ASXL1 gene mutation].

Objective: To examine the survival rates and clinical characteristics of people with newly discovered non-M(3) acute myeloid leukemia (AML) who carry the ASXL1 gene mutation. Methods: From January 2016 to April 2021, the clinical information of patients with newly diagnosed non-M(3) AML at Shandong University's Qilu Hospital was retrospectively examined, and their clinical characteristics and survival were compared and analyzed. Gene mutation was detected by next-generation sequencing. Results: ① The study included 256 AML patients who were initially diagnosed and had complete data, including 47 cases of ASXL1 gene mutation-positive (ASXL1(+)) patients and 209 cases of ASXL1 gene mutation-negative (ASXL1(-)) patients. All patients were divided into three groups: elderly (≥60 years old, n=92) , middle-aged (45-59 years old, n=92) , and young (≤44 years old, n=72) . ②WBC, and age were higher in patients with ASXL1 mutations compared to ASXL1(-) patients, while complete response after the first round of treatment (CR(1)) was lower (P<0.05) . In the elderly group, WBC and the proportion of aberrant cells in nuclear cells in ASXL1(+) patients were higher than those in ASXL1(-) patients (P<0.05) . In the young group, the WBC of ASXL1(+) patients was higher than that of ASXL1(-) patients (z=-2.314, P=0.021) . ③IDH2 mutation and ASXL1 mutation was related (P=0.018, r=0.34) . In ASXL1(+) patients, the proportion of peripheral blasts in the high VAF group (VAF>40% ) was higher than that in the low VAF group (VAF<20% ) , and the proportion of aberrant nuclear cells was higher in the duplication and replacement mutation patients than in the deletion mutation patients (P<0.05) . ④The overall survival (OS) and progression-free survival (PFS) of ASXL1(+) patients were shorter than those of ASXL1(-) patients (median, 10 months vs 20 months, 10 months vs 17 months; P<0.05) . The proportion number of aberrant cells in nuclear cells (≥20% ) , complex karyotypes, and TET2 mutation were all independent risk variables that had an impact on the prognosis of ASXL1(+) patients, according to multivariate analysis (P<0.05) . Conclusion: ASXL1-mutated non-M(3) AML patients have higher WBC in peripheral blood, a higher proportion of aberrant cells in nuclear cells, lower CR(1) rate, and shorter OS and PFS. Additionally, a poor prognosis is linked to higher VAF, duplication, and substitution mutations in the ASXL1 gene, as well as the high proportion of aberrant cells in nuclear cells, complex karyotype, and TET2 mutation.

[Application of electrophysiological monitoring in acoustic neuroma resection].

Objective: To investigate the neuroprotective effect of facial nerve monitoring on acoustic schwannoma resection and its impact on prognosis. Methods: Eighty patients with acoustic schwannomas were enrolled in our study in the past 2 years and randomly divided into a monitoring group and a non-monitoring group. Tumor size was measured by MRI, and the general condition of the patients were analyzed. The preoperative hearing loss was evaluated, and the facial numbness, post-group related symptoms, and facial paralysis grade were also evaluated before surgery. The monitoring group performed facial nerve monitoring during the operation of auditory schwannomas resection, while the non-monitoring group did not. Both groups decided to perform total or subtotal resection according to the actual conditions during the operation. The hearing status, facial numbness, posterior group related symptoms and facial paralysis grade were evaluated 3 days after surgery, and the prognosis Glasgow outcome score (GOS) was evaluated 1 month after surgery. Results: There were no significant differences between two groups in terms of general condition and preoperative evaluation. There was also no significant difference in surgical methods. But the incidence of facial numbness in monitoring group (42.9%, 15/35) was significantly lower than that in non-monitoring group (86.7%, 39/45) (P<0.001). The facial paralysis grade in monitoring group (17/Ⅰ, 9/Ⅱ, 8/Ⅲ, 1/Ⅳ) was also significantly lower than that of non-monitoring group (1/Ⅰ, 18/Ⅱ, 17/Ⅲ, 9/Ⅳ) (P<0.001). The prognostic score (GOS) in monitoring group (4.60±0.55) was significantly higher than that in non-monitoring group (3.78±0.67)(P<0.001). Conclusion: Facial nerve monitoring can provide better neuroprotection on acoustic schwannoma resection, avoid facial nerve injury, and improve the prognosis quality of life significantly.

[Minimally invasive surgery for centrally located lung cancers].

Minimally invasive surgery helps enhance postoperative recovery and improve quality of life of the patients by minimizing surgical trauma and decreasing incisional pain. Minimally invasive pulmonary resection, including both video-assisted thoracoscopic surgery and robotic surgery, is mainly used for surgical management of peripheral early stage lung cancers. Because of tumor location, lymph node involvement, and treatment modalities, surgery for central lung cancers is often technically demanding. Open thoracotomy is still the dominant approach for these tumors, especially when complex procedures such as sleeve lobectomy or pneumonectomy are needed. With the advent of surgical techniques, minimally invasive techniques have started to be tried in treatment of central lung cancers. Initial results have proven their feasibility and safety in sleeve lobectomy and pneumonectomy, showing a great potential of minimally invasive surgery in the future. Further study is necessary to prove its functionally superiority and oncological equivalence to open surgery, so that more lung cancer patients could benefit for minimally invasive surgery.

[A twin study of genetic and environmental influences on relationship between attention deficit and anxiety/depression in children and adolescents].

Objective: To understand the genetic and environmental influences on the relationship between attention deficit and anxiety/depression in children and adolescents. Methods: A total of 1 062 same-sex twins aged 6-18 years were included in this study. A parent-rated child behavior checklist (CBCL) was used in the assessment. Software Mx was used to fit the univariate model of structural equation. The relationship between attention deficit and anxiety/depression was analyzed through bivariate genetic modeling. Results: The genetic factor had influence on the relationship between attention deficit and anxiety/depression (r(g)=0.48). Shared and non-shared environmental correlation scores of attention deficit and anxiety/depression were 0.86 and 0.14 respectively. Conclusion: Common genetic and shared environmental influences can explain the relationship between attention deficit and anxiety/depression in children and adolescents.

Lengthening the pedicle of the rectus abdominis myocutaneous flap for repair of upper chest and neck defects.

INTRODUCTION The aim of this study was to investigate whether the pedicle of the rectus abdominis flap can be lengthened by resecting the inferior costal cartilage segments or associated muscle when repairing upper body defects. A formula was generated that calculates the expected increase in pedicle length. METHODS Thirty patients underwent computed tomography. The width and thickness of the third to seventh inferior costal cartilage segments as well as the width of the respective intercostal spaces were recorded. Four patients underwent reconstruction of an upper body defect with the relevant flap. RESULTS The expected mean increases in pedicle length were 4.07cm (standard deviation [SD]: 0.31cm) and 4.63cm (SD: 0.54cm) following resection of the left and right sides respectively of the seventh inferior costal cartilage segment, 7.99cm (SD: 0.49cm) and 10.82cm (SD: 0.23cm) following resection of the left and right sides respectively of the sixth and seventh inferior costal cartilage segments while resection of the fourth to seventh inferior costal cartilage segments would equate to increases of 17.48cm (SD: 0.62cm) and 22.05cm (SD: 0.21cm) for the left and right sides respectively. In four patients who required reconstruction, three flaps survived without problems but one flap developed partial necrosis. CONCLUSIONS Resecting inferior costal cartilage segments or associated muscle can lengthen the pedicle of the rectus abdominis flap for reconstruction of defects on the upper chest and neck.

[The establishment and application of internal quality control system for real-time quantitative PCR detection of BCR-ABL (P210) transcript levels].

Objective: To set internal quality control system of BCR-ABL (P210) transcript levels for real-time quantitative PCR (RQ-PCR). Methods: Using K562 cells and HL-60 cells, we prepared high- and low-level BCR-ABL internal quality control substance. The BCR-ABL (P210) transcript levels of internal quality control substance have been determined for 184 times together with clinical samples from August 2013 to October 2015. The slope rate, intercept and correlation coefficient of standard curve were calculated according to different reagent lots (lots number 20130303, 20131212, 20140411 and 20150327 are called R1、R2、R3 and R4 for short respectively), and the detection results of quality control substance were calculated according to different reagent lots and quality control substance lots (lots number 20130725, 20140611 are called Q1、Q2 for short respectively). Then the results were analyzed by Levey-Jennings quality control chart combined with Westgard multi-rules theory. Results: ①We analyzed the slope rate and intercept of standard curve. Fifty-three times of the R1 reagent detection, 80 times of the R3 reagent detection and 14 times of the R4 reagent detection were all under control. For 37 times detection of R2 reagent, the slope rate was out of control for 6 times. It was lower than x-s for the 2-8 tests and upper the average for the 12-37 tests. The intercept was out of control for 9 times, upper the x+s for the 1-8 tests and lower the average for the 12-37 tests. ② According to the detection results of quality control substance, for Q1 quality control substance, 49 tests by R1 reagent were under control, and 1 out of 23 tests by R2 reagent was out of control. For Q2 quality control substance, 14 tests by R2 reagent detection, 72 tests by R3 reagent detection and 14 tests by R4 reagent were all under control. Conclusion: The preparation of high- and low-level quality control substance using K562 and HL-60 cells was convenient and the detection results were reliable and stable. The application of quality control substance combined with slope rate and intercept in the internal quality control may contribute to quality assurance for quantitative detection of BCR-ABL (P210) transcript levels.

Family history and prior allergies of cancers and the risk of adult leukemia in shandong province, china.

BACKGROUND: A case-control study was carried out to investigate the roles of prior allergies and family history of cancers and their interaction in the etiology of adult leukemia. METHODS: Prior allergies status and family history of cancers in first-degree relatives were compared between 131 incident leukemia cases and 206 hospital-based controls. Odds ratios (OR) were estimated using an unconditional regression model taking into account potential confounding factors. RESULTS: Significant association between adult leukemia and prior allergies and family history of cancer (OR=2.09, 95% CI: 1.22-3.58 for prior allergies; and OR=2.35, 95% CI: 1.09-5.03 for family history of cancer, OR=15.88, 95% CI: 1.77-142.55 for both the two factors (+), respectively) was found after adjusting for potential confounding factors. CONCLUSION: Prior allergies and family history of cancers may be risk factors for adult leukemia; their interaction was likely to be synergistic rather than additive for the risk of leukemia.

Novel and recurrent COL2A1 mutations in Chinese patients with spondyloepiphyseal dysplasia.

Spondyloepiphyseal dysplasia (SED) is an autosomal dominant skeletal dysplasia characterized by short stature, abnormal epiphyses and flattened vertebral bodies. SED is mainly caused by mutations in the gene encoding the type II procollagen α-1 chain (COL2A1). We looked for mutations in COL2A1 in three unrelated Chinese families with SED. Putative mutations were confirmed by RFLP analysis. We identified three missense mutations (p.G504S, p.G801S and p.G1176V) located in the triple-helical domain; p.G801S and p.G1176V are novel mutations. The p.G504S mutation has been associated with diverse phenotypes in previous studies. Our study extends the mutation spectrum of SED and confirms a relationship between mutations in the COL2A1 gene and clinical findings of SED.

Identification of novel and recurrent mutations in the calcium binding type III repeats of cartilage oligomeric matrix protein in patients with pseudoachondroplasia.

Pseudoachondroplasia is an autosomal dominant osteochondrodysplasia characterized by disproportionate short stature, joint laxity, and early onset osteoarthrosis. Pseudoachondroplasia is caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP). We looked for mutations in the COMP gene in three sporadic Chinese pseudoachondroplasia patients and identified two novel mutations, c.1189G>T (p.D397Y) and c.1220G>A (p.C407Y), and one recurrent mutation, c.1318G>C (p.G440R), in the calcium binding type III repeats of COMP. This study confirms the relationship between mutations of the COMP gene and clinical findings of pseudoachondroplasia; it also provides evidence for the importance of the calcium binding domains to the functioning of COMP.

The prevalence of childhood overweight/obesity and the epidemic changes in 1985-2000 for Chinese school-age children and adolescents.

This paper describes the nationwide prevalence of childhood overweight/obesity in Chinese urban population. Data sets of boys and girls aged 7-18 yrs were collected from the series of Chinese national surveillance on students' constitution and health between 1985 and 2000 were divided into five socioeconomic groups, while WGOC BMI-reference was used as definitions of overweight and obesity. In 2000, the prevalence of childhood obesity/overweight in the coastal big cities, followed by that of the coastal middle/small cities, had reached the average level of the developed countries. The prevalence of obesity was low in most of the inland cities at an early stage of epidemic overweight. The epidemic manifested a gradient distribution in groups, which was closely related to socioeconomic status of the populations. A dramatic and steady increasing trend was witnessed among all sex-age subgroups in these urban groups, and the increments in obesity/overweight are exceptionally high in recent 5 years, and the prospect of epidemic obesity in China is in no way optimistic. Preventive program should be focused on the improvement of the balance between caloric intake and energy expenditure, and interventions aimed at changing children's life styles.

[Analysis of mass minimization of Thermoelectric Integrated Membrane Evaporation Subsystem in waste water processing].

OBJECTIVE: To minimize in the system level the designed mass of Thermoelectric Integrated Membrane Evaporation Subsystem (TIMES) of Environment Control Life Support System (ECLSS) in manned spacecraft, when the requirement of the production rate of fresh water and its hygiene is fulfilled. METHOD: According to the characteristics of the operational process of TIMES, the physical and mathematical model for fluid flow, heat transfer and mass composition in its main parts were established to investigate numerically the relation between the system mass and those parameters associated with the structure and operation of the system. RESULT: The system mass depended not only on the structural parameters and operational parameters of TIMES, but also on the operational characteristics of power subsystem and thermal control subsystem. The relative mass covered a large part of the system mass. CONCLUSION: There existed an optimum of the number of thermoelectric cooling parts and flow rate of circular waste water of the TIMES when the designed system mass was minimum. Moreover, higher condensation pressure in the system contributed to lower system mass.

Age at spermarche and comparison of growth and performance of pre- and post-spermarcheal Chinese boys.

The prevalence of first ejaculation emission (spermarche) in Chinese Han boys in 1995 was considered. The subjects were 86,744 Han boys 9 through 18 years randomly selected from 28 provinces. Median spermarcheal ages (MSAs) were 14.4 and 14.6 years for urban and rural boys, respectively, and 14.3, 14.6, and 14.7 years for the boys of 1st, 2nd, and 3rd socioeconomic classes, respectively. Two environmental factors, ecological and socioeconomic, had strong influence upon MSAs. Eight indicators of somatic growth and motor ability were compared between pre- and post-spermarcheal boys of the same age. Post-spermarcheal boys were advanced in body size, shape, and physiological function during early and middle puberty, but most of the difference disappeared by 16 years. Pre-spermarcheal boys in a given age group were more linear and had more potential for increasing leg length into late adolescence. Within an age group, post-spermarcheal boys had advanced performances in several tasks requiring endurance, strength, and power around the age of maximum growth, 13-15 years. At older ages, the groups did not differ.

Serum IGF-binding protein-6 and prostate specific antigen in breast cancer.

OBJECTIVE: Recent studies have demonstrated the presence of the IGF-binding proteins (IGFBPs) and prostate specific antigen (PSA), an IGFBP protease. in human breast tissue. We sought to investigate the differences in serum IGFs, IGFBP-1, -3 and -6, and PSA between patients with surgically proven breast cancer and patients with benign breast disease. DESIGN AND METHODS: Concentrations of IGFs, IGFBP-1, -3 and -6, and PSA were determined in the sera from 57 patients with breast cancer (CA), and 46 women with benign breast disease (BBD) using immunoassays for IGFs and IGFBPs and an ultrasensitive ELISA for PSA. RESULTS: The mean (+/- S.E.M.) serum IGFBP-6 level in the CA group, 127 (16) ng/ml, was statistically significantly lower than in the BBD group, 157 (10) ng/ml (P = 0.016). Patients with CA had an elevated geometric mean serum PSA level of 0.018 (range: 0.0015-0.107) ng/ml, compared with 0.007 (range: 0.0015-0.019) ng/ml in women with BBD (P = 0.025). Mean serum IGFBP-1 concentrations were significantly lower in the CA group, 16 (2) ng/ml, versus 37 (4) ng/ml in the BBD group (P = 0.001). Mean serum IGFBP-3 concentrations were also lower in the CA group versus the BBD group, at 1981 (65) ng/ml, versus 2603 (140) ng/ml (P = 0.002) respectively. In the CA group, statistically significant correlations between PSA and IGFBP-6 (r = 0.413; P = 0.001), and between PSA and IGFBP-1 (r = -0.329; P = 0.021) were seen. Differences in IGF-I and -II between the two groups were not statistically significant. CONCLUSION: Lower serum concentrations of IGFBP-6, -3 and -1, but higher PSA concentrations were seen in the breast cancer group, and collectively these would suggest that there is an increase in bioavailable IGF-I in breast cancer.

Urinary 2/16 alpha-hydroxyestrone ratio: correlation with serum insulin-like growth factor binding protein-3 and a potential biomarker of breast cancer risk.

Metabolism of estradiol occurs via two mutually exclusive hydroxylative pathways, yielding metabolites of divergent biological properties. 2-hydroxyestrone (2OHE1) is anti-estrogenic while 16 alpha-hydroxyestrone (16 alpha OHE1) is a potent estrogen. The ratio of 2OHE1 to 16 alpha OHE1 (2/16 alpha-OHE1 ratio) represents the net in vivo estrogenic activity. In this study, we sought to determine if the urinary 2/16 alpha-OHE1 ratio could be a predictor of breast cancer risk and the factors which influence this ratio. Variables analysed included age at diagnosis, menopausal status, parity, use of oral contraceptives, body mass index, serum levels of insulin-like growth factor-I (IGF-I), IGF binding proteins (BPs) and the presence of breast cancer. Serum and urine were collected from 65 breast cancer patients and 36 controls after an overnight fast. Urinary estrogen metabolites were measured by enzyme immunoassays while serum levels of IGF-I, BP-1 and BP-3 were determined by immunoradiometric assays. 2OHE1 levels and 2/16 alpha-OHE1 ratios were significantly lower (P < 0.05) while 16 alpha OHE1 levels were higher (P < 0.01) in cancer patients. Multiple linear regression analysis showed that levels of urinary metabolites were influenced by parity and breast carcinoma. 2/16 alpha-OHE1 ratio correlated positively with serum BP-3 level (P = 0.03). By multiple logistic regression, 2/16 alpha-OHE1 ratio was the most significant factor predictive of breast cancer. The odds ratio for women with higher 2/16 alpha-OHE1 ratios was 0.10 (0.03-0.38, 95% confidence interval). In conclusion, the profile of urinary estradiol metabolites was distinctly altered in breast cancer patients. In addition, BP-3 may be a potential mechanism by which estradiol metabolites influence breast cancer progression. As 16 alpha OHE1 has been shown to initiate neoplastic transformation of mammary epithelial cells, the 2/16 alpha-OHE1 ratio may serve as a biomarker of increased risk of breast cancer.

Tamoxifen alters levels of serum insulin-like growth factors and binding proteins in postmenopausal breast cancer patients: a prospective paired cohort study.

BACKGROUND: Recent data suggest that tamoxifen may act by altering serum levels of insulin-like growth factors (IGFs) and their binding proteins (BPs). This prospective paired cohort study evaluated the influence of tamoxifen on serum levels of IGFs and BPs in postmenopausal patients with breast cancer. METHODS: Blood was collected from 32 postmenopausal patients with breast cancer before and during tamoxifen therapy for at least 6 months. All patients had undergone primary surgery. Serum concentrations of IGF-I, IGF-II, BP-1, and BP-3 were determined by immunoradiometric assays, and Western ligand blots provided a semiquantitative measurement of BP-2, BP-3, and BP-4. Statistical analysis was performed by paired Student's t-test. RESULTS: Mean serum IGF-1 level was significantly lower after tamoxifen treatment (pretreatment: 116.2 ng/mL+/-13.6 [SEM] vs. posttreatment: 77.5 ng/mL+/-7.8; P=.003). In contrast, mean IGF-II levels increased from 651.5+/-62.2 ng/mL to 812.5+/-35.1 ng/mL during treatment (P=.006). Posttreatment levels of BP-1 (92.9 ng/mL+/-7.5) were significantly higher compared to the pretreatment values (28.1 ng/mL+/-4.7; P <.001). Serum concentration of BP-3 also was elevated (pretreatment: 2228.1 ng/mL+/-145.2 vs. posttreatment: 3539.1 ng/mL+/-172.3; P <.001). Densitometric measurements showed a similar significant increase in BP-3 (P <.001) as well as BP-4 (P=.017) after hormonal therapy. Levels of BP-2 were not influenced by tamoxifen treatment. CONCLUSIONS: These significant alterations in serum concentrations of IGFs and BPs with tamoxifen therapy suggest that the IGF system is a potential mechanism by which tamoxifen exerts its growth inhibitory effect on breast carcinomas.

Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) has mitogenic properties for breast cancer cell lines and has been proposed to be an important factor in breast carcinogenesis. We hypothesized that differences in IGF-1 or its binding proteins might increase susceptibility to breast cancer. This case-control study was designed to investigate whether patients with breast cancer have altered levels of either IGF-1 or its intermediary modulatory proteins, the IGF binding proteins (BP). METHODS: Serum was collected from 90 patients (63 with breast cancer and 27 with benign breast disease) after an overnight fast and before surgery. IGF-1, BP1, and BP3 levels were determined by immunoradiometric assays. In a subset of 66 patients, Western ligand blots were also performed for a semiquantitative measurement of functioning BP levels. A forward stepwise logistic regression model to adjust for other confounding variables (age, menopausal status, parity, age at menarche, use of oral contraceptives, history of breast biopsy, family history of breast cancer, hormone replacement therapy, and body-mass index) was used in the multivariate analysis. RESULTS: Serum IGF-1 levels were similar in cases and controls. However, levels of BP3 (p < 0.001), BP4 (p < 0.01), and BP1 (p < 0.05) were significantly associated with risk of breast cancer. The level of BP3 was the most significant factor predictive of breast cancer. The odds ratio for breast cancer in women with BP3 levels >2066 ng/ml was 0.18 (95% CI, 0.05-0.55). Correspondingly, women with BP1 levels higher than 39 ng/ml had an odds ratio of 0.21 (95% CI, 0.07-0.68) for breast cancer. When considering only cancer patients (n = 63), decreasing levels of BP4 (p < 0.01) and increasing levels of BP1 (p < 0.02) were significantly associated with progesterone receptor positivity (PR+) in the tumor. The odds ratio of PR+ in patients with BP1 levels higher than 34 ng/ml was 7.49 (95% CI, 1.5-37.4). Better grade of tumor (well and moderately differentiated) was observed in patients with higher levels of BP3 (p < 0.03). CONCLUSIONS: Distinct differences in BP profiles exist among patients with breast cancer and also among those with high-grade, hormonal receptor-negative tumors. These findings suggest that the bioavailability of IGF-1 as mediated by its binding proteins may participate in both breast carcinogenesis and selection of more aggressive breast carcinomas.

Loss of c-met protooncogene in primary and metastatic sites of breast cancer.

BACKGROUND: It has been proposed that clones of tumor cells acquire higher metastatic potential as a result of specific genetic alterations. This study was designed to determine the role of the c-met protooncogene in systemic spread by comparing the loss of the c-met protooncogene between primary and metastatic breast carcinomas. METHODS: Only patients who had not received chemotherapy or radiotherapy in the preceding 6 months were included in this study. Histologically proven malignant tissue was obtained from the primary tumor, involved nodes, and distant metastatic and recurrent tumors of patients with breast carcinomas. Allelic loss of the c-met protooncogene in tumor tissue was determined by Southern blotting using a polymerase chain reaction-generated 347-bp human met-H probe. Restriction digestion was performed using Taq I and Msp I, with the patient's lymphocyte DNA as controls. RESULTS: Of 52 patients, lymphocyte DNA from 36 patients was heterozygous for the c-met protooncogene (69% informative). Forty-six tumors from these 36 patients were analyzed. Four of 30 primary tumors (13%) showed allelic loss of c-met. Of the nine nodal metastases examined, three (33%) showed allelic loss of the c-met protooncogene. Of seven distant metastatic breast tumors or recurrent disease, two (29%) showed allelic loss (both in patients with skin metastasis in the chest wall). CONCLUSIONS: Allelic loss of the c-met protooncogene was detected in both primary (13%) and metastatic sites (31%) of breast cancer. Although a higher proportion of allelic loss of c-met was noted in nodal and distant/recurrent disease, the difference when compared with the primary tumor was not statistically significant. These findings indicate a limited role of the c-met protooncogene in breast cancer metastases.