Associations between clinical-pathological parameters and biomarkers,HER-2, TYMS,RRMI, and 21-gene recurrence score in breast cancer

BackgroundChemotherapy is the predominant treatment option for patients with breast cancer. Selection of patients according to biomarker will improve chemotherapy efficacy. In the present study, we examined the relations of the expression of candidate genes and 21-recurrence score (RS) results to patients’ demographic characteristics, histopathological factors, and outcomes.MethodsA total of 146 patients were enrolled in this study. The patients underwent 21-gene RS testing. In addition, expressions of candidate genes, TYMS, RRM1, TUBB3, TOP2A, PTEN, were detected. Information was obtained on age, tumor size, TMN stage, tumor grade, and status of Ki-67, HER2, ER and PR. The treatment information on the type of endocrine therapy was also obtained.ResultsResults clearly showed that the 21-gene RS significantly correlated with the TNM stage of breast cancer (P = 0.047). The RS also correlated with the number of sentinel lymph node (P = 0.038). The pathological type of tumors was strongly associated with the expression of RRM1 (P < 0.015), and slightly correlated with TYMS (P = 0.095) and tumor size (P = 0.061). Further analysis showed that TYMS and RRM1 were two independent factors affecting the disease progression of patients. Besides, for HER-2 stain, staining of grade 2 or above significantly increased the risk of disease progression.ConclusionOur studies showed that TNM stage and sentinel lymph node were important clinical parameters correlated with 21-gene RS results. Also, RRM1, TYMS and HER2 expressions were independent factors associated with disease progression in breast cancer patients. Future study is warranted to investigate the usefulness of these genes in treatment efficacy.     

Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium-DTPA-enhanced MRI and localized 19F MRS pharmacokinetic studies of 5-fluorouracil

Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of the drug in the tumor and by the amount of intracellular uptake, metabolic activation and catabolism, as well as other factors. The first aim of this study was to investigate the predictive value of DCE-MRI with the contrast agent Gd-DTPA for tumor response to first-line chemotherapy in patients with liver metastases of colorectal cancer. The second aim was to investigate the predictive value of 5-fluorouracil (FU) uptake, retention and catabolism as measured by localized (19)F MRS for tumor response to FU therapy. Since FU uptake, retention and metabolism may depend on tumor vascularization, the relationship between (19)F MRS and the DCE-MRI parameters k(ep), K(trans) and v(e) was also examined (1). In this study, 37 patients were included. The kinetic parameters of DCE-MRI, k(ep), K(trans) and v(e), before start of treatment did not predict tumor response after 2 months, suggesting that the delivery of chemotherapy by tumor vasculature is not a major factor determining response in first-line treatment. No evident correlations between (19)F MRS parameters and tumor response were found. This suggests that in liver metastases that are not selected on the basis of their tumor diameter, FU uptake and catabolism are not limiting factors for response. The transfer constant K(trans), as measured by DCE-MRI before start of treatment, was negatively correlated with FU half-life in the liver metastases, which suggests that, in metastases with a larger tumor blood flow or permeability surface area product, FU is rapidly washed out from the tumor.     

Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis

Methotrexate (MTX), widely used in the treatment of rheumatoid arthritis (RA), inhibits dihydrofolate reductase (DHFR) and folate-dependent enzymes. Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) are key enzymes in the folate metabolism and both have been shown to be polymorphic affecting the enzyme activity. To clarify the association between these genetic variations and MTX-related toxicity and efficacy in the treatment of RA, a total of 167 Japanese individuals with RA, including 52 and 63 patients treated with low-dose MTX with or without adverse effects, respectively, and 52 patients without MTX administration were analyzed. Among the 93 patients treated with MTX for >2 months, significantly more patients homozygous for the triple-repeat allele of the polymorphism in the promoter region of the TYMS gene required higher dose of MTX compared to those having at least a double-repeat allele (P=0.033). The incidence of > or =50% improvement in the serum CRP level was significantly higher in patients homozygous for the deletion allele of the polymorphism in the 3'-untranslated region (UTR) of the TYMS gene (P=0.0383). The allele frequency of the insertion/deletion polymorphism in the TYMS 3'UTR in Japanese was significantly different from that in Caucasians (P<0.0001), as was the tandem-repeat polymorphism in its promoter region. On the other hand, MTHFR C677T and A1298C polymorphisms showed no association with MTX-related toxicity or efficacy. Our results suggest that the genotyping for the TYMS polymorphisms may become a useful indicator in determining the appropriate dose of MTX in patients with RA.     

Consolidation with high-dose combination alkylating agents with bone marrow transplantation significantly improves disease-free survival in hormone-insensitive metastatic breast cancer in complete remission compared with intensive standard-dose chemotherapy alone.

We conducted this study to determine event-free and overall survival among women with hormone-insensitive or hormone-resistant metastatic breast cancer receiving consolidation with high-dose chemotherapy (HDC) and hematopoietic support versus no further chemotherapy after intensive induction chemotherapy. Eligible patients received induction doxorubicin, 5-fluorouracil, and methotrexate (AFM) for 2 to 4 cycles. Women in complete remission were randomized to immediate HDC with cyclophosphamide, cisplatin, and carmustine followed by autologous hematopoietic support or to no further therapy. Patients on the observation arm of therapy were offered salvage HDC at the time of relapse. Partial responders to AFM were offered immediate HDC. A total of 425 patients were enrolled onto the study. The median event-free survival for women randomized to induction therapy alone was 3.8 months, compared with 9.7 months for women who completed HDC (P < .006). Of the patients randomized to observation, 5 (10%) of 51 remain event free, compared with 13 (26%) of 49 patients who underwent immediate HDC (P = .03). Of women converted to a complete response by salvage HDC after a partial response to AFM, overall survival was similar to that in women randomized to immediate HDC. Follow-up is now in excess of 5 years. The 5-year event-free survival is 15% (95% confidence interval, 12%-18%), and the 5-year overall survival is 20% (95% confidence interval, 17%-25%). Immediate HDC after a complete response to AFM produced some durable long-term responses in hormone-insensitive/-resistant metastatic breast cancer. Salvage HDC converted 30% of partial responders to complete responders with similar survivals. The addition of novel targeted therapies to intensive-dose chemotherapy regimens may further improve survival in metastatic breast cancer.     

Biochemotherapy with immunomodulating pineal hormones other than melatonin: 5-methoxytryptamine as a new oncostatic pineal agent

Several experiments have demonstrated that pineal gland plays a physiological anticancer role. Melatonin (MLT), its most investigated hormone, is a natural anticancer agent. However, MLT would not be the only endocrine molecule responsible for the anticancer property of the pineal gland. In fact, another pineal indole hormone, the 5-methoxytryptamine (5-MTT), has appeared to exert in vitro an antitumour activity superior to that of MLT itself. Previous studies have already shown the therapeutic anticancer action of MLT in association with chemotherapy also in human neoplasms. This study was performed to evaluate the influence of 5-MTT at physiological doses (1 mg/day orally during light phase) on the efficacy of chemotherapy with cisplatin plus etoposide in advanced non-small cell lung cancer patients with respect to that obtained in patients treated by chemotherapy alone or chemotherapy plus pharmacological doses of MLT (20 mg/day orally during the dark phase of the day). The study included 100 patients, who were randomised to receive chemotherapy alone or in association with MLT or 5-MTT. The overall response rate achieved in both patients concomitantly treated with MLT or 5-MTT was significantly higher with respect to that obtained in patients treated with chemotherapy alone. Moreover, both MLT and 5-MTT significantly reduced some chemotherapy-related toxicities, namely thrombocytopenia and neurotoxicity. This preliminary study shows that less known pineal hormone 5-MTT may exert at low doses the same anticancer therapeutic effect in association with chemotherapy, which may be obtained by pharmacological doses of the most investigated pineal hormone MLT.     

Molecular mechanisms of drug resistance

Resistance to chemotherapy limits the effectiveness of anti-cancer drug treatment. Tumours may be intrinsically drug-resistant or develop resistance to chemotherapy during treatment. Acquired resistance is a particular problem, as tumours not only become resistant to the drugs originally used to treat them, but may also become cross-resistant to other drugs with different mechanisms of action. Resistance to chemotherapy is believed to cause treatment failure in over 90% of patients with metastatic cancer, and resistant micrometastic tumour cells may also reduce the effectiveness of chemotherapy in the adjuvant setting. Clearly, if drug resistance could be overcome, the impact on survival would be highly significant. This review focuses on molecular mechanisms of drug resistance that operate to reduce drug sensitivity in cancer cells. Drug resistance can occur at many levels, including increased drug efflux, drug inactivation, alterations in drug target, processing of drug-induced damage, and evasion of apoptosis. Advances in DNA microarray and proteomic technology, and the ongoing development of new targeted therapies have opened up new opportunities to combat drug resistance. We are now able to characterize the signalling pathways involved in regulating tumour cell response to chemotherapy more completely than ever before. This will facilitate the future development of rational combined chemotherapy regimens, in which the newer targeted therapies are used in combination with cytotoxic drugs to enhance chemotherapy activity. The ability to predict response to chemotherapy and to modulate this response with targeted therapies will permit selection of the best treatment for individual patients.     

Phase II study of paclitaxel, cisplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer

This phase II study evaluated the efficacy and safety of combination chemotherapy with paclitaxel, cisplatin, and 5-fluorouracil (5-FU) in advanced gastric cancer. Patients with histologically confirmed gastric adenocarcinoma were eligible for the study. Paclitaxel (175 mg/m(2)) and cisplatin (75 mg/m(2)) were given as a 1-hr intravenous infusion on day 1, followed by 5-FU (750 mg/m(2)) as a 24-hr continuous infusion for 5 days. This cycle was repeated every 3 weeks. Forty-five eligible patients (median age, 56 yr) were treated in this way. Of the 41 patients in whom efficacy was evaluable, an objective response rate (ORR) was seen in 51.2% (95% CI, 0.35-0.67), a complete response in two, and a partial response in 19 patients. The median progression free survival was 6.9 months (95% CI, 5.86-7.94 months), and the median overall survival was 12.7 months (95% CI, 9.9-15.5). The main hematological toxicity was neutropenia and greater than grade 3 neutropenia was observed in twelve patients (54%). Febrile neutropenia developed in three patients (6.8%). The major non-hematological toxicities were asthenia and peripheral neuropathy, but most of patients showed grade 1 or 2. In conclusion, combination chemotherapy with paclitaxel, cisplatin, and 5-FU is a promising regimen, and was well tolerated in patients with advanced gastric cancer.     

Thymostimulin increases natural cytotoxic activity in patients with breast cancer

The effect of thymostimulin on the Natural Killer (NK) cytotoxic activity of peripheral blood mononuclear cells (PBMC) was investigated in 15 patients with breast cancer after finishing or during chemotherapy (CAF) and in 10 healthy controls. PBMC from these subjects were incubated in the presence of thymostimulin for varying periods of time (18 h or 5 days), and then used as effector cells against ⁵¹Cr-radiolabeled NK-sensitive (K-562) and NK-resistant (JY) target cells in cytotoxicity assays. No significant differences were observed between the NK-activity from breast cancer patients and healthy controls. Thymostimulin induced a dose- and time-dependent cytotoxic enhancing effect on the cytotoxic activity of PBMC from these patients against NK-sensitive K562 target cells. The thymostimulin (1000ng/ml) significantly enhanced cytotoxic activity in PBMC from breast cancer patients who had previously received chemotherapy (p = 0.0277) against NK-sensitive cells. This increase was not statistically significant neither in PBMC from patients receiving chemotherapy nor in healthy controls (p > 0.05 in both cases). The incubation of PBMC from patients with breast cancer was not associated to a significant enhancement of the cytotoxic activity against NK-resistant target cells (p > 0.05). We also found that thymostimulin could synergize with interleukin-2 in inducing NK cytotoxic activity in PBMC after 18h of culture (p=0.0277). In conclusion, we have demonstrated that thymostimulin enhances the natural killer cytotoxic activity of PBMC from patients with breast cancer who have previously received chemotherapy.     

Outpatient-basis chemotherapy of oxaliplatin, 5-fluorouracil, and leucovorin as first-line treatment for patients with metastatic or recurrent colorectal cancer

The objectives of the present study were to evaluate the efficacy and safety of an outpatient-basis chemotherapy of oxaliplatin, 5-fluorouracil, and leucovorin as the first-line treatment for patients with advanced colorectal cancer. Forty-three histologically confirmed patients with metastatic or recurrent colorectal cancer were enrolled. The chemotherapy consisted of oxaliplatin 85 mg/m(2) as a 2-hr infusion on day 1, plus leucovorin 30 mg/m(2) over 10 min, followed by bolus 5-fluorouracil 400 mg/m(2) and an 8-hr infusion of 5-fluorouracil 600 mg/m(2) on days 1 and 2 (modified FOLFOX4), all of which were administered on an outpatient basis every 2 weeks. The median age was 58 yr (range 33-72 yr), and 25 (58.1%) patients had metastatic diseases. Eventually, 39 patients were assessable for efficacy and all assessable for toxicity. Four (9.3%) complete responses and 11 (25.6%) partial responses were confirmed, giving an overall response rate of 34.9% (95% CI; 20.0-49.7%). The median time to progression and median overall survival for all patients was 6.1 months and 17.4 months, respectively. Grade 3/4 neutropenia occurred in 2 patients (4.7%) and febrile neutropenia was observed in 1 patient (2.3%). Modified FOLFOX4, an outpatient-basis regimen, was found to be well-tolerated and effective as the first-line chemotherapy in patients with advanced colorectal cancer.     

miR-429在食管鳞癌中的表达及对细胞增殖迁移的影响

 目的 评价重组改构人肿瘤坏死因子（rmhTNF）对晚期胃癌的临床疗效，并观察其不良反应。 方法 试验设计为前瞻性随机对照研究。64例晚期胃癌患者随机分为2组，化疗＋rmhTNF组（rmhTNF组）40例，单纯化疗组24例。两组化疗方案相同：氟尿嘧啶500 mg/m2，第1~5天给药；多柔比星40 mg/m2，第1天给药；丝裂霉素 6 mg/m2，第1天给药；21 d为1个周期，连用2个周期。rmhTNF组第1~7、11~17天另行肌内注射rmhTNF 400万U/m2。疗效评价分为完全缓解（CR）、部分缓解（PR）、好转（MR）、稳定（SD）和进展（PD），有效率=（CR+PR）/总例数×100%；临床受益率=（CR+ PR+MR+SD）/总例数×100%；并进行治疗前后生存质量评分（Karnofsky评分）比较。毒性反应根据WHO抗癌药急性及亚急性毒性分级标准评估。 结果 单纯化疗组2例未完成2个周期治疗中途退出，其余62例按计划完成试验，可评价疗效；64例患者均可评价不良反应。有效率rmhTNF组为17.5%（7/40），单纯化疗组为4.5% （1/22），但组间差异无统计学意义（P=0.144）；临床受益率rmhTNF组为80.0%（32/40），单纯化疗组为54.5%（12/22），组间差异有统计学意义（P=0.036）。rmhTNF组治疗后Karnofsky评分为87.2±7.5，高于治疗前的83.0±7.9（P =0.001）；单纯化疗组Karnofsky评分治疗后无明显变化（治疗前为84.1±8.0，治疗后为83.2±7.8）；两组治疗后Karnofsky评分比较，差异有统计学意义（P= 0.049）。rmhTNF肌内注射给药的不良反应主要为注射局部疼痛、注射局部红肿硬结、畏冷寒战、骨肌肉疼痛、发热、感冒样症状等，但程度较轻，患者均可耐受。 结论 rmhTNF与化疗联合应用治疗晚期胃癌，有助于提高患者的近期有效率，改善患者的一般状况和生活质量；rmhTNF局部肌内注射给药毒副作用较轻，患者可以耐受。     

Behavioral treatment for the anticipatory nausea and vomiting induced by cancer chemotherapy

The nausea and vomiting experienced by one in four cancer patients in anticipation of chemotherapy is probably a learned response to treatment. To determine whether behavioral approaches for altering learned responses might be useful treatments for these symptoms, we compared the effects of "systematic desensitization" (a behavioral treatment in which relaxation is learned as a response to situations in which patients have had anticipatory nausea and vomiting) with those of counseling and of no treatment. Sixty ambulatory cancer patients with anticipatory nausea and vomiting before their third and fourth chemotherapy treatments were randomized equally to the three groups. Significantly more patients receiving desensitization reported no anticipatory nausea before their fifth and sixth chemotherapy treatments than patients given counseling (P less than 0.05) or no treatment (P less than 0.01). Desensitized patients also reported significantly less severe anticipatory nausea (P less than 0.01) and vomiting (P less than 0.05) and a shorter duration of anticipatory nausea (P less than 0.01). We conclude that systematic desensitization appears to have an antiemetic effect in cancer patients who receive chemotherapy, and may be useful in the management of these problems.     

Monoclonal Antibodies Targeting Vascular Endothelial Growth Factor

The use of monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) pathway has been a significant addition to cancer therapy. One of the VEGF family members, VEGF-A (commonly referred to as VEGF), has been demonstrated to be important in angiogenesis. Although the mechanism of action of these antibodies is still under study, the anti-VEGF antibody bevacizumab has been approved for treatment of various solid cancers including colorectal, lung, and breast cancers as well as glioblastoma and renal cell carcinoma. Addition of bevacizumab to chemotherapy as adjuvant therapy in colorectal cancer did not improve disease-free survival. Bevacizumab is being tested in other clinical settings such as adjuvant therapy, maintenance therapy, and in combination with both chemotherapy and other targeted agents such as the epidermal growth factor receptor kinase inhibitor erlotinib. In addition to bevacizumab, other antibody-based therapies targeting the VEGF pathway are being tested. Ramucirumab and IMC-18F1 are monoclonal antibodies that target the VEGF receptors VEGFR-2 and VEGFR-1, respectively. Aflibercept (VEGF-Trap), a peptide-antibody fusion targeting VEGF ligand, is being tested in clinical trials. Much research is focused on identifying biomarkers to predict which patients will benefit from anti-VEGF therapy. Recent results suggest that VEGF single nucleotide polymorphisms may be predictive of patient response to bevacizumab. Improved imaging modalities such as dynamic contrast-enhanced MRI (DCE-MRI) can better characterize the efficacy of anti-angiogenic agents. As anti-VEGF treatments such as bevacizumab have been integrated into the treatment of many different types of cancers, the development of bevacizumab-resistant tumors has become more common. Recent studies show that targeting other angiogenesis signaling pathways such as platelet-derived growth factor-C (PDGF-C), Bombina variagata peptide 8 (Bv8, also known as prokineticin-2), and VEGFR-3 may lead to enhanced response in anti-VEGF resistant tumors. In the future, tailored treatments consisting of combinations of chemotherapy, other targeted therapies, and anti-angiogenesis agents will hopefully result in better patient outcomes.     

Combination of oxaliplatin, fluorouracil, and leucovorin in the treatment of fluoropyrimidine-pretreated patients with metastatic colorectal cancer

There has been no standard therapy for patients with metastatic colorectal cancer who have failed to first-line fluorouracil-based treatment. The present study was designed to assess the efficacy and toxicities of a combination of oxaliplatin, 5-fluorouracil (5-FU) and leucovorin in fluoropyrimidine-pretreated patients with metastatic colorectal cancer. Chemotherapy consisted of oxaliplatin 85 mg/m2 on day 1, followed by leucovorin 20 mg/m2 and 5-FU 1,200 mg/m2 on days 1 and 2. Treatment courses were repeated every two weeks. Thirty-nine patients were enrolled in this study. All patients previously received fluoropyrimidine-based chemotherapy. Thirty-one patients were assessable for response and 33 for treatment toxicity. Six patients required dose reduction of 5-FU due to grade III/IV cytopenia. Nausea/vomiting and peripheral neuropathy were common non-hematologic toxicities. Overall response rate was 42.0% including 3 complete response and 10 partial response. The median response duration was 91 days (range, 28-224+). The median duration of progression-free survival was 132 days (range, 40-308). A combination of oxaliplatin, 5-FU, and leucovorin showed high response rate in fluoropyrimidine-pretreated patients with metastatic colorectal cancer, but the duration of response was relatively short. It may be worthwhile to explore its therapeutic potential in the first-line treatment setting.     

Clinical relevance of angiopoietin-1, angiopoietin-2, and their receptor Tie-2 expression in acute myeloid leukemia

The angiogenic-related factors: angiopoietin-1 and -2 and their receptor Tie-2 have wide-ranging effects on tumor behavior that includes angiogenesis and, inflammation. These multifaceted pathways present a potential target in developing novel inhibition strategies for cancer therapy. The present work aimed at detecting the prevalence of expression of: angiopoietin-1, angiopoietin-2, and their receptor Tie-2 in 56 Egyptian de novo acute myeloid leukemia (AML) patients by conventional RT-PCR to verify the prognostic impact of their expression on the response to induction chemotherapy. Thirty age- and sex-matched healthy volunteers were subjected to the same analysis as a control group. High expression of angiopoietin-1 (Ang-1) was detected in the patient group but not the control group. AML patients expressing angiopoietin-2 (Ang-2) either solely or in combination with high Ang-1 and/or Tie-2 showed unfavorable response to induction chemotherapy; either failed induction or death during induction. These data provide evidence that the alternation of angiopoietin balance in favor of Ang-2 may play a critical role in the pathophysiology of AML. Furthermore, positive pre-therapeutic expression of Ang-2 indicates valiable unfavorable prognostic marker in AML patients and may be used as a prognostic tool in the risk-adaptive management of AML.     

新辅助化疗对局部进展期乳腺癌患者T淋巴细胞亚群及NK细胞免疫功能的影响

目的:探讨局部进展期乳腺癌患者新辅助化疗前、后T淋巴细胞亚群及NK细胞免疫功能的变化。方法:采用流式细胞术检测54例局部进展期乳腺癌患者新辅助化疗前后的静脉血T淋巴细胞亚群及NK细胞免疫功能。美国癌症联合会(American Joint Commitree on Cancer,AJCC)肿瘤分期为Ⅱb期(仅T3N0M0)和Ⅲ期(不包括N3),静脉血于第1周期新辅助化疗治疗前及第3周期化疗后21日抽取,淋巴细胞亚群检测包括:T(CD3+,CD4+,CD8+),NK(CD56+,CD16+),经过3周期新辅助化疗CEF方案(表柔比星、环磷酰胺和5-氟尿嘧啶),根据新辅助化疗临床效果评价分为2组,化疗有效组38例(CR和PR),化疗无效组16例(SD和PD),并与正常体检健康者(40例)作比较。结果:乳腺癌患者治疗前CD4+、CD4+/CD8+明显低于对照组(P<0.01),NK细胞明显低于对照组(P<0.05),新辅助化疗后,有效组总CD3+、CD4+、CD4+/CD8+、NK细胞较治疗前均显著升高(P<0.05),CD8+降低(P<0.05);无效组CD3+、CD4+/CD8+及NK细胞较治疗前显著降低(P<0.05),而CD8+升高(P<0.05)。结论:局部进展期乳腺癌患者免疫功能低下,有效的辅助化疗能提高患者的免疫功能,定期监测免疫功能对指导临床治疗有意义。     

Incidence of pathologic complete response in women treated with preoperative chemotherapy for locally advanced breast cancer: correlation of histology,hormone receptor status,Her2/Neu,and gross pathologic findings

Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer and is used increasingly for large operable breast cancer. The aim of this study was to assess the rate of pathologic complete response (pCR) in our patient population with locally advanced breast cancer and identify predictive factors for pCR after neoadjuvant chemotherapy. We studied a cohort of 205 patients and compared histologic features and biomarkers in the pretreatment biopsy with the corresponding pathologic response in the subsequent resection specimen. A pCR was defined as the absence of any microscopic evidence of tumor in the mastectomy specimen and axillary lymph node dissection. The tumor size was reduced in 60% of patients; 16 patients had a pCR. Histologic grade, histologic type, and hormone status did correlate with a pathologic response. None of the 29 invasive pure micropapillary carcinomas had a pCR. Pathologic complete response among Mexican patients with locally advanced breast cancer is low (8%), and the presence of invasive pure micropapillary carcinoma could be an independent predictor for pCR.     

乳腺癌新辅助化疗后临床评价与病理评价的差异分析

目的 探讨乳腺癌新辅助化疗后,临床疗效评价与病理评价之间存在差异的病理学基础.方法 收集中国医学科学院肿瘤医院2005年6月至2007年12月施行乳腺癌新辅助化疗的209例.新辅助化疗前均行核芯针穿刺活检.化疗结束后4周内实施乳腺癌根治术.新辅助化疗前后均对乳腺原发灶进行临床体检、乳腺X线检查和(或)超声检查.实施新辅助化疗后,依实体瘤的疗效评价标准(RECIST,1.1版)对乳腺癌原发灶进行临床疗效评价,依Miller和Payne(MP)分级系统进行病理评价.应用SPSS 15.0软件分析临床评价与病理评价的相关性.结果 (1)新辅助化疗后依临床体检结果进行临床评价:完全缓解33例,部分缓解124例,疾病稳定41例,疾病进展11例.(2)新辅助化疗前后均行乳腺X线检查87例,依乳腺X线检查进行临床评价:完全缓解8例,部分缓解42例,疾病稳定37例.(3)新辅助化疗后MP分级病理评价:1级14例,2级35例,3级106例,4级36例,5级18例.(4)临床体检相关的临床评价与病理评价存在统计学相关性(x2=33.668,P=0.001),乳腺X线检查相关的临床评价与病理评价存在统计学相关性(x2=22.404,P=0.004).(5)新辅助化疗病理评价与X线检查相关临床评价存在差异的病理学改变有:残存浸润癌以脉管瘤栓为主要表现形式;伴有大片黏液湖形成的黏液腺癌;导管内癌残存,伴明显沙砾样钙化及周围组织的沙砾样钙化;间质结节状纤维化等.结论 乳腺癌新辅助化疗的临床评价与病理评价存在统计学相关性.两者之间的差异有相应的病理学基础.伴有大片黏液湖形成的黏液腺癌、导管内癌的残存伴沙砾样钙化及间质结节状纤维化可能是临床评价低估治疗疗效的原因之一;而残存癌表现为脉管瘤栓可能是临床评价高估治疗疗效的原因之一.     

乳腺癌新辅助化疗后临床评价与病理评价的差异分析

目的 探讨乳腺癌新辅助化疗后,临床疗效评价与病理评价之间存在差异的病理学基础.方法 收集中国医学科学院肿瘤医院2005年6月至2007年12月施行乳腺癌新辅助化疗的209例.新辅助化疗前均行核芯针穿刺活检.化疗结束后4周内实施乳腺癌根治术.新辅助化疗前后均对乳腺原发灶进行临床体检、乳腺X线检查和(或)超声检查.实施新辅助化疗后,依实体瘤的疗效评价标准(RECIST,1.1版)对乳腺癌原发灶进行临床疗效评价,依Miller和Payne(MP)分级系统进行病理评价.应用SPSS 15.0软件分析临床评价与病理评价的相关性.结果 (1)新辅助化疗后依临床体检结果进行临床评价:完全缓解33例,部分缓解124例,疾病稳定41例,疾病进展11例.(2)新辅助化疗前后均行乳腺X线检查87例,依乳腺X线检查进行临床评价:完全缓解8例,部分缓解42例,疾病稳定37例.(3)新辅助化疗后MP分级病理评价:1级14例,2级35例,3级106例,4级36例,5级18例.(4)临床体检相关的临床评价与病理评价存在统计学相关性(x2=33.668,P=0.001),乳腺X线检查相关的临床评价与病理评价存在统计学相关性(x2=22.404,P=0.004).(5)新辅助化疗病理评价与X线检查相关临床评价存在差异的病理学改变有:残存浸润癌以脉管瘤栓为主要表现形式;伴有大片黏液湖形成的黏液腺癌;导管内癌残存,伴明显沙砾样钙化及周围组织的沙砾样钙化;间质结节状纤维化等.结论 乳腺癌新辅助化疗的临床评价与病理评价存在统计学相关性.两者之间的差异有相应的病理学基础.伴有大片黏液湖形成的黏液腺癌、导管内癌的残存伴沙砾样钙化及间质结节状纤维化可能是临床评价低估治疗疗效的原因之一;而残存癌表现为脉管瘤栓可能是临床评价高估治疗疗效的原因之一.     

Correlation between clinical pathologic factors and activity of 5-FU-metabolizing enzymes in colorectal cancer.

INTRODUCTION: Orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) are initial key enzymes in the 5-fluorouracil (5-FU) metabolic pathway. The expression levels and activities of these three enzymes play important roles in the response of cancer patients to 5-FU-based chemotherapy. PURPOSE: The purpose of this study was to investigate the relationship between the activities of 5-FU metabolic enzymes and clinicopathologic factors in colorectal cancer. METHODS: We measured the activities of OPRT, DPD, and TS in colorectal cancer tissues. We also investigated the correlations between the activities of these three enzymes and clinicopathologic factors (histological type, depth of tumor invasion, extent of lymph node metastasis, Dukes' stage, lymphatic invasion, and vascular invasion). We examined 100 patients with surgically resected colorectal cancer. RESULTS: Poorly differentiated adenocarcinoma showed significantly higher DPD activities than did moderately differentiated or well-differentiated adenocarcinoma. In patients with lymph-node metastasis, OPRT activity was significantly lower than in patients without lymph-node metastasis. No significant relation was found between TS activity and histological type, depth of tumor invasion, extent of lymph node metastasis, Dukes' stage, lymphatic invasion, or vascular invasion. CONCLUSION: The response to 5-FU may be poor in patients with lymph-node metastasis, because of low OPRT activity, and in patients with poorly differentiated adenocarcinoma, because of high DPD activity.