膀胱癌尿液生物学标记物的研究进展

在世界范围内膀胱癌是一种常见的恶性肿瘤，发病率在美国居男性第四位，女性第十二位，死亡率男性列第七位，女性第十五位。在我国，其发病率和死亡率均占泌尿男生殖系统肿瘤的首位。膀胱癌生物学标记物（bladder cancer biomarkers）是膀胱肿瘤发生、发展过程中产生的相关生物学活性物质，随尿液排出体外。检测膀胱癌生物学标记物，有助于肿瘤的早期诊断、疗效观察和预后评估。虽然在临床上膀胱镜和尿细胞学检查仍然是膀胱癌诊断和监测的金标准，但尿液生物学标记物正日益受到重视，新的标记物不断被发现并在临床使用。美国食品药品管理局（federal drug and food administration，FDA）已经批准了4种尿液生物学标记物用于膀胱癌的临床诊断和（或）监测，更多的标记物还在研究当中，其中一些有望用于临床。     

膀胱肿瘤标记物的研究进展

膀胱肿瘤在我国泌尿系统肿瘤中位居第一,且有极高的复发率,因而早期诊断和监测复发就很重要。尿细胞学检查和膀胱镜是目前诊断监测膀胱癌的传统方法,但都有局限性。膀胱癌生物学标记因其简单无创和敏感性等特点被人们寄予厚望。但目前研究的一些肿瘤标记物如BTA、BTAstat、BTA-TRAK以及NMP22等由于种种原因尚不能取代传统的尿细胞学和膀胱镜。因而人们一直在努力寻找一种更理想的肿瘤标记物。本文就目前膀胱肿瘤标记物的研究进展作一综述。     

DNA甲基化与胆囊癌

DNA甲基化是真核生物的正常修饰方式,异常的DNA甲基化与肿瘤的发生发展密切相关,具有重要生物学意义.胆囊癌中肿瘤相关基因启动子的异常甲基化,作为表观遗传标记物,在胆囊癌的发病、诊治、疗效观察及预后判断等方面可能发挥重要作用.     

肾癌预后分子标记物研究新进展

手术治疗是惟一可能治愈肾癌的方法。由于肾癌生物学行为不同,近30％的患者术后肿瘤复发。因此,寻找敏感的肾癌标记物用以早期发现肿瘤,并能判断患者预后,早期发现复发,指导个体化治疗具有重要的临床意义。已发现多种标记物与肾癌预后有关,例如缺氧诱导因子1-α、碳酸苷酶IX、P53、Ki67、存活素、B7-H4、血清淀粉样蛋白A和核基质蛋白22等。这些标记物分布于肾癌组织、血及尿中。分析其表达可以判断患者预后。     

原发性肝癌的现代治疗

原发性肝癌是恶性程度较高的肿瘤,初次就诊时肿瘤常属于中晚期,切除率低,发现肿瘤后患者的生存期往往非常短暂。但近半个世纪以来,随着腹部Ｂ超的出现、各种影像学方法的发展及ＡＦＰ等肿瘤标记物检测的应用,使肝癌的早期发现及根治切除成为可能。在对肝癌的生物学行...     

Survivin在膀胱癌中的研究进展

Survivin是凋亡抑制蛋白家族成员之一 ,几乎在所有人类肿瘤中都有不同程度的表达 ,在正常分化成熟的组织中不表达 (胸腺、生殖腺除外 ) ,具有调节细胞周期、抑制细胞凋亡的作用。它是一个有潜在价值的肿瘤标记物和肿瘤治疗的新靶点 ,本文就其生物学特点及在膀胱癌中的研究现状进行综述。     

Survivin在膀胱癌中的研究进展

Survivin是凋亡抑制蛋白家族成员之一，几乎在所有人类肿瘤中都有不同程度的表达，在正常分化成熟的组织中不表达(胸腺、生殖腺除外)，具有调节细胞周期、抑制细胞凋亡的作用。它是一个有潜在价值的肿瘤标记物和肿瘤治疗的新靶点，本文就其生物学特点及在膀胱癌中的研究现状进行综述。     

泌尿系肿瘤增殖细胞核抗原研究进展

肿瘤细胞增生活性与肿瘤生物学行为有关．增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇ　ｃｅｌｌ　ｎｕｃｌｅａｒ　ａｎｔｉｇｅｎ　，ＰＣＮＡ）是第一个可大规模用于常规石蜡包埋组织检测肿瘤细胞增生活性的生物标记物，本文对ＰＣＮＡ分子生物学，ＰＣＮＡ作为生物标记物的可行性，优越性及其在泌尿系肿瘤物，本文对ＰＣＮＡ分子生物学，ＰＣＮＡ作为生物标记物的可行性，优越性及其在泌尿系肿瘤中的意义作一综述。     

泌尿系肿瘤增殖细胞核抗原研究进展

肿瘤细胞增生活性与肿瘤生物学行为有关。增殖细胞核抗原（ＰＣＮＡ）是第一个可大规模用于常规石蜡包埋组织检测肿瘤细胞增生活性的生物标记物，本文对ＰＣＮＡ分子生物学，ＰＣＮＡ作为生物标记物的可行性，优越性及其在泌尿系肿瘤中的意义作一综述。     

前列腺癌浸润转移的肿瘤标记研究进展

研究前列腺癌肿瘤标记物的目的在于了解肿瘤生物学行为，预测浸润转移潜能，对判断预后有重要意义。本文综述了五类瘤标研究进展。     

Prospects for gene therapy and lymphokine therapy for metastatic melanoma.

Conventional treatment of cancer, especially for patients with metastatic melanoma tumor, is often ineffective. Immunotherapy and recently introduced gene therapy have revolutionized the treatments of patients with metastatic melanoma tumor. Use of biological response modifiers, such as interleukins and interferons, have been found to enhance therapeutic benefits to patients with malignant melanoma. Initial studies with a high-dose interleukin-2 (IL-2) therapy have proved effective in patients with melanoma tumor, although a variety of systemic toxicities were observed. A low-dose IL-2 continuous infusion has shown a similar response in patients with melanoma tumor, but produced lesser toxicity. The low-dose IL-2 therapy has been studied with an adoptive transfer combined with either autologous lymphokine activated killer cells or autologous tumor infiltrating lymphocytes (TIL). IL-2 in combination with chemotherapeutic agents such as flavone acetic acid, dacarbazine, and cyclophosphamide have also been studied in patients with metastatic melanoma. Results have shown a moderate response in patients with metastatic melanoma. TIL therapy, however, has been shown to result in higher objective regression due to potent tumor-specific killing and tumor-specific targeting characters of the TIL. The tumor targeting nature of the TIL creates the possibility of using TIL as a vehicle to deliver gene product specifically to tumor tissue. Safety and toxicity of gene-transduced TIL were addressed by the use of neomycin-resistant, gene-transduced TIL in patients with metastatic melanoma. We also investigated the use of vaccinia oncolysate therapy by using the viral oncolysate prepared with IL-2 gene encoded vaccinia virus. Preliminary studies with murine hepatic metastases colon model have shown encouraging results.     

Malignant melanoma in the thymus

A case of malignant melanoma in the thymus is reported. Diagnostic imaging demonstrated a left anterior mediastinal mass in a patient with giant pigmented nevus without malignant change. Histologic and cytologic specimens obtained from the tumor revealed that the tumor was malignant melanoma. Surgery revealed malignant melanoma in the left lobe of the thymus. Many cell nests of pigmented nevi were observed throughout the thymus. The malignant melanoma was thought to have originated from the nevocellular nevus in the thymus. This is the first report of malignant melanoma in the thymus.     

Oral malignant melanoma detected after resection of amelanotic pulmonary metastasis

INTRODUCTIONSolitary pulmonary metastasis from oral malignant melanoma is very rare.PRESENTATION OF CASEWe demonstrated a 84-year-old patient with a lung nodule that was diagnosed as malignant melanoma by video-assisted thoracoscopic resection. Because primary pulmonary malignant melanoma was extremely rare, the tumor was thought to be a metastasized from an occult primary lesion. A detailed physical examination revealed a black tumor in the oral cavity, and this was suspected to have been the primary. Resection of the hard palate tumor and dissection of the cervical lymph nodes were performed. The patient was simply followed up without further therapy at his request, and he died one year after surgery due to bleeding from a pleural metastasis of malignant melanoma.DISCUSSIONPrimary melanoma of the oral cavity is rare, accounts for 0.5% of all oral cancers, and 0.8–1.8% of all melanomas. Because of absence of symptoms in the early stage of the disease and the presence of the tumor in relatively obscure areas of the oral cavity, the diagnosis is unfortunately often delayed. In view of the rarity of primary lung melanoma, when lung tumor was diagnosed as malignant melanoma, detailed physical examination of the entire skin and mucosa including the oral cavity was necessary.CONCLUSIONOral malignant melanoma was very rare, but oral cavity should be examined when the pulmonary nodule was diagnosed as malignant melanoma.     

Melanoma-specific cytotoxic T cells generated from peripheral blood lymphocytes. Implications of a renewable source of precursors for adoptive cellular immunotherapy.

Cytotoxic T lymphocytes (CTL) specific for autologous human melanoma have been generated in vitro from peripheral blood lymphocytes (PBL) of five patients with resectable stage II malignant melanoma. The PBL were cultured with 5u/ml recombinant IL-2 and were repeatedly stimulated with irradiated fresh or cultured autologous tumor cells. Cytotoxicity was determined by four-hour chromium release assays. Specific cytotoxicity developed in 30 to 40 days, after three or four stimulations with tumor. The PBL-derived CTL are CD3+ and are mixed for CD4+ and CD8+ phenotypes. They lysed autologous melanoma and failed to lyse allogeneic melanoma, K562, or autologous lymphocytes. The lysis of autologous tumor was maintained for more than 4 months. The cells proliferated in response to autologous, but not allogeneic melanoma cells, in a dose-dependent manner. Lysis of the autologous tumor target was inhibited with w6/32, a monoclonal antibody to HLA Class I antigens. It is concluded that PBL may serve as a plentiful and renewable source of precursor cells for the generation of autologous tumor-specific CTL, which may be useful in specific adoptive cellular immunotherapy of melanoma.     

Primary malignant melanoma of the anterior mediastinum in a child

Primary malignant melanoma of the mediastinum is extremely rare. We report a case not previously reported of primary malignant melanoma located in the mediastinum in a 11-year-old boy. The tumor could not be completely resected as a result of extensive invasion of the large blood vessels. Histologically, the tumor was heavily pigmented and composed of vague fascicles of spindle cells intermingled with epithelioid cells. Immunohistochemical analysis showed vimentin, S-100 protein, Melan-A, and HMB-45 immunoreactivity in most of the tumor cells. Nearly 50% of the tumor cells were also positive for p53. It is suggested that primary malignant melanoma of the anterior mediastinum may have a histogenetic relationship to the recently described aggregates of nevus cells in the thymus or mediastinal lymph nodes.     

Successful treatment of triple primary tumor

INTRODUCTIONThe occurrence of multiple primary tumors is rare. Only limited number of cases with triple malignancy have been reported. We report here a rare case of a woman presented synchronous triple tumors, in her lung, breast, skin.PRESENTATION OF CASEA 56-year-old woman presented with invasive ductal carcinoma of breast, non-small cell lung cancer and malignant melanoma. The patient undergone mastectomy and malignant melanoma tumor excision on-site. After operation stereotactic radiotherapy was given to her lung tumor. Six course of chemotherapy was given to her. She is alive with no progression.DISCUSSIONThe patient was diagnosed with melanoma and staging by FDG/PET. There is not any study about routine using PET/CT in the melanoma staging.CONCLUSIONThis is a very rare synchronous triple tumor case.     

Serum cartilage-derived retinoic acid-sensitive protein (CD-RAP) levels in swarm rat chondrosarcoma.

Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a new protein that was isolated from bovine articular chondrocytes and human melanoma cell lines (melanoma inhibitory protein or MIA). In normal tissue its expression is limited to cartilage, and in morbid tissue to melanoma, chondrosarcoma, and breast cancer. Serum levels of CD-RAP/MIA correlate with the progression of malignant melanoma, but there have been no reports on chondrosarcoma. Here, it was first demonstrated by RT-PCR and immunohistological methods that CD-RAP was expressed in tissue from a Swarm rat chondrosarcoma that was used as an experimental model. The course following tumor transplantation and changes in serum CD-RAP after tumor excision were then observed to investigate whether serum CD-RAP could be used as a marker of tumor activity. Consequently, serum CD-RAP in control rats tended to decrease as the animal grew, whereas it rose in proportion to tumor proliferation in rats that had received a tumor graft. Serum CD-RAP levels dropped rapidly following excision of the tumor in a group of tumor-excised rats. In those rats which had a recurrence following excision of the tumor, serum CD-RAP rose prior to the appearance of the tumor. Serum CD-RAP thus sensitively reflected tumor onset and proliferation, so that it appeared to be an effective marker of tumor activity for Swarm rat chondrosarcoma.     

Radiculopathy due to malignant melanoma in the sacrum with unknown primary site

Melanoma is an interesting tumor, showing the appearance of metastasis without any trace of its primary lesion. To report a very rare case of malignant melanoma in the sacrum with unknown primary origin. The authors present a case of a 52-year-old man who was admitted with increasing lower back, left buttock, and left lower extremity pain, and dysuria. Plain radiograph, computed tomography scan, and magnetic resonance imaging revealed a destructive lesion in the sacrum and left ilium, which infiltrated the spinal canal and sacroiliac joint. The tumor cells were immunoreactive for HMB-45. The pathological diagnosis was malignant melanoma. No obvious primary malignant melanoma was detected on the skin surface, on the oral or anal mucosa, or in the fundus oculi. Following radiotherapy and chemotherapy, the severe buttock pain disappeared and the patient was able to walk without impediment. However the patient died nine months after initial diagnosis. Malignant melanoma in the sacrum with an unknown primary site, showing S1 radiculopathy is reported for the first time. The melanoma could have been a metastatic tumor of the sacrum, although the primary site was not detected. The incidence of primary melanoma is increasing faster than any other cancer. Thus treatment of patients with spinal metastasis of melanoma is an important challenge for orthopedic surgeons.

     

Malignes Melanom

Malignant melanomas have one of the highest increases in incidence among malignancies. There are four histological types: superficial spreading melanoma, nodular melanoma, acrolentiginous melanoma and lentigo maligna melanoma. The TNM classification considers depth of infiltration (Clark’s level), vertical tumor thickness (Breslow’s thickness), ulceration of the primary tumor, satellites and in-transit metastases as well as regional lymph node and distant metastases. An adequate margin of clearance is important in primary resection. Sentinel lymph node biopsy is relevant in all melanomas with a Breslow tumor thickness >1 mm without clinically suspicious lymph nodes. In the case of lymph node metastases therapeutic dissection is recommended, in patients with in-transit metastases of the extremities hyperthermic isolated limb perfusion with cytostatic agents may be indicated. Resection of distant metastases can be useful if only one site is affected or a R0 resection is expected to be achieved. Adjuvant, neoadjuvant and palliative procedures, such as radiotherapy, chemotherapy and immunotherapy are additional treatment options.     

Sentinel lymph node biopsy for the T1 (thin) melanoma: is it necessary?

The use of sentinel lymph node biopsy for the T1 melanoma is controversial. Recent reports have demonstrated that certain T1 melanomas are at increased risk for early regional metastases and late recurrence when compared with all thin melanomas. The purpose of this study was to review the authors' experience with wide excision and sentinel lymph node biopsy for certain patients with T1 melanoma. A retrospective analysis of 34 patients with T1 melanoma was completed over a 3-year period. Indications for sentinel lymph node biopsy included a Breslow thickness of less than or equal to 1 mm a Clark level of III or IV tumor ulceration, or tumor regression. Twenty-four patients met these criteria (13 men and 11 women). Mean age was 47.6 years (range, 23-88 years). Mean tumor thickness for all patients was 0.69 mm (range, 0.3-1.0 mm), 0.61 mm for the Clark level III patients (N = 15), and 0.72 mm for the Clark level IV patients (N = 9). Tumor ulceration was present in 1 patient and histological regression was present in 2 patients. Regional lymph node metastases were confirmed histologically in 2 of 24 patients (8.3%) in whom the thickness of the melanoma was 0.9 mm and 1 mm. Both patients have died of metastatic melanoma. No recurrence has been demonstrated in the remaining 22 patients at the 2 to 5-year follow-up. Current indications for sentinel lymph node biopsy for patients with T1 melanoma include tumors associated with Clark level IV or V invasion, ulceration, regression, a positive deep margin on initial biopsy, or previous melanoma. Acral lentiginous melanoma associated with at least a Clark level III invasion warrant sentinel lymph node biopsy. Superficial spreading or nodular melanoma larger than 0.9 mm should include sentinel lymph node biopsy regardless of other associated histological factors.