Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitor-1 in cartilage-forming osteal tumors.

The expression of MMP-1, -2, -9 and TIMP-1 was studied in 10 benign cartilage-forming osteal tumors (5 osteochondromas and 5 chondromas) and 39 chondrosarcomas (14 central, 4 periosteal, 7 dedifferentiated, and 14 secondary tumors). No expression of MMP and TIMP-1 was detected in benign cartilage-forming osteal tumors. In chondrosarcomas, the expression of MMP-1 was detected in 84.6%, of MMP-2 in 71.8, of MMP-9 in 97.4, and of TIMP-1 in 82.4% cases, the levels of expression of these markers varied from 10 to 60%. The expression of MMP-1 was not associated with patient gender, maximum size and degree of differentiation of the tumor, but was linked with age. The expression of MMP-1 was more often detected in central and dedifferentiated chondrosarcomas; the expression of MMP-1(+) was significantly associated with 3-year relapse-free and 5-year overall survival of the patients. The expression of MMP-1 in the tumor was associated with unfavorable course of the disease. The values of MMP-2 expression in chondrosarcomas did not reflect the main clinical morphological characteristics of the disease and its prognosis. The level of MMP-9 protein expression in chondrosarcomas ≥40% is prognostically unfavorable, while <40% is a favorable factor for 3-year relapse-free survival. The risk of disease relapse within 1 year after the beginning of therapy was maximum in T3 tumors with expression of MMP-9 protein ≥40%. No relationships between the parameters of TIMP-1 expression in chondrosarcomas and the main clinical morphological characteristics of the disease and its prognosis were detected.

A randomized phase II study of bortezomib and pemetrexed, in combination or alone, in patients with previously treated advanced non-small-cell lung cancer.

BACKGROUND: This is a phase II randomized study to evaluate the efficacy and safety of bortezomib and pemetrexed alone or in combination, in patients with previously treated advanced non-small-cell lung cancer (NSCLC). The primary end point was assessment of response rate. METHODS: A total of 155 patients were randomized (1:1:1) to pemetrexed (500mg/m(2)) on day 1 plus bortezomib (1.6mg/m(2)) on days 1 and 8 (Arm A) or pemetrexed (500mg/m(2)) on day 1 (Arm B) or bortezomib (1.6mg/m(2)) on days 1 and 8 (Arm C) of a 21 day cycle. Response rate was assessed by investigators using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and toxicity assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system. RESULTS: Response rate was 7% in Arm A, 4% in Arm B, and 0% in Arm C; disease control rates were 73%, 62%, and 43%, respectively. Median overall survival was 8.6 months in Arm A, 12.7 months in Arm B, and 7.8 months in Arm C; time to progression was 4.0 months, 2.9 months, and 1.4 months, respectively. Most common reported adverse events >/=grade 3 were neutropenia (19%), thrombocytopenia (15%), and dyspnea (13%) in Arm A, neutropenia (10%) in Arm B, and dyspnea (13%) and fatigue (10%) in Arm C. CONCLUSION: In previously treated NSCLC the addition of bortezomib to pemetrexed was well tolerated but offered no statistically significant response or survival advantage versus pemetrexed alone, while bortezomib alone showed no clinically significant activity.

Development of a new G-CSF product based on biosimilarity assessment.

BACKGROUND: Zarzio, a new recombinant human granulocyte colony-stimulating factor (filgrastim), was evaluated in healthy volunteers and neutropenic patients in phase I and III studies. PATIENTS AND METHODS: Healthy volunteers in randomized, two-period crossover studies received single- and multiple-dose s.c. injections of 1 microg/kg (n = 24), 2.5 microg/kg (n = 28), 5 microg/kg (n = 28), or 10 microg/kg (n = 40), as well as single-dose i.v. infusions of 5 microg/kg (n = 26), of Zarzio or the reference product (Neupogen). Filgrastim serum levels were monitored; pharmacodynamic parameters were absolute neutrophil count (all studies) and CD34(+) cells (multiple-dose studies). Supportive efficacy and safety data were obtained from an open phase III study in 170 breast cancer patients undergoing four cycles of doxorubicin and docetaxel (Taxotere) chemotherapy, receiving Zarzio (300 or 480 microg) as primary prophylaxis of severe neutropenia. RESULTS: The results of the studies in healthy volunteers confirm the comparability of the test and reference products with respect to their pharmacodynamics and pharmacokinetics. Confidence intervals were within the predefined equivalence boundaries. In the phase III study in breast cancer patients, the administration of Zarzio was efficacious and safe, triggering no immunogenicity. CONCLUSION: The results of these studies demonstrate the biosimilarity of Zarzio with its reference product Neupogen.

[Soft tissue chondroma].

The paper gives a rare case of soft tissue chondroma in a 55-year-old female woman who has unsuccessfully received physiotherapeutic procedures for more than 6 months due to misdiagnosis. The patient detected the tumor herself. Clinical and X-ray diagnostic difficulties are considered. Differential diagnosis was made between synovial chondromatosis and chondrosarcoma. A correct diagnosis could be established only at open tumor biopsy. The neurovascular fascicle, tendons, and an intrinsic group of shoulder muscles could be preserved during radical surgery. The problems in the morphological diagnosis of extraskeletal chondroma are discussed in detail. The results of organ-preserving resection are presented.

[Dedifferentiated chondrosarcoma: problems of diagnosis and treatment].

In 2001-2007, Moscow cancer hospital sixty-two examined 77 patients with chondrosarcoma (including consultative cases). The dedifferentiated form of the tumor was confirmed in 10 (13%) cases. Recurrences and metastases were observed in 3 patients. Radical surgery could be performed in 5 patients, including interileoabdominal exarticulation in 4 patients. Immunohistochemical studies provide a way of specifying the nature of one of the tumor components. Ultrastructural data on the components of dedifferentiated chondrosarcoma are first presented in the Russian literature. Fine-needle biopsy and trepan-biopsy may give an incorrect guide to choosing treatment policy. The experience in performing combined therapy for this unusual tumor is first presented in the Russian literature and drug pathomorphism has been studied. Radical surgery remains to be the method of choice in treating patients with dedifferentiated chondrosarcoma; however, the capabilities of multidrug therapy and irradiation should not be ignored in this form of the tumor.

[Osteocartilaginous exostoses (osteochondromas)].

Osteochondroma is the most common true bone neoplasm formed by a cartilage capped bony projection arising on the external surface of a bone containing a marrow cavity that is continuous with that of the underlying bone. Osteochondromas generally arise in the bones preformed by cartilage. Osteochondromas may be solitary and multiple. Most reported cases have been in the first 3 decades with no known sex predilection. The lesion has three layers - perichondrium, cartilage and bone. The cartilage cap is usually less than 2.0 cm thick, superficial chondrocytes are clustered, the ones close to the transition to the bone resemble a growth plate, they are organized into chords and undergo enchondrial ossification. Loss of the architecture of cartilage, wide fibrous bands, myxoid change, increased chondrocyte cellularity, mitotic activity, significant chondrocyte atypia and necrosis are all features that may indicate secondary malignant transformation.

[Abnormal (bizarre) paraostial osteochondromatous proliferation (Nora's disease)].

Bizarre paraostial osteochondromatous proliferation (BPOP) is a reactive process composed of bone and cartilage attached to the surface of a bone, the condition was first described by Nora et al. as a reactive proliferation involving small bones. A case of a 76-year-old male represents the first description of BPOP in the Russian literature. The patient has a history of trauma, the duration of symptoms being more than a year. Xray study shows suspected secondary chondrosarcoma. The benign space-occupying lesion BPOP is verified after wedge resection of the phalanx. The described condition seems to occur more frequently than reported in the literature. Current imaging techniques and histological study permit avoidance of diagnostic errors and correct choice of the scope of treatment.

[Osteochondrosarcoma: clinical and morphological comparisons].

A total of 109 patients with chondrosarcoma were operated on in 2005-2007. Classical primary chondrosarcoma was verified in 77 cases; secondary and periosteal chondrosarcomas were confirmed in 28 and 4 patients, respectively. By analyzing their findings and the data available in the literature, the authors considered the current problems in the classification and diagnosis of the most common types of cartilaginous malignancies. New techniques, including cytogenetic assay, significantly alleviate this problem. However, the most precise cytogenetic assays are expensive and not always accessible for usual oncological care. The principal criteria in practice are a clinical picture, the results of radiation studies, and the standard histological method that establishes the differentiation of chondrosarcoma, the extent of a process, and the specific features of tumor growth. Immunohistochemical assay are of no crucial importance. In some cases, fine-needle biopsy may provide useful information to make a decision on treatment policy.

[Chondroblastoma].

Chondroblastom, benign cartilage tissue neoplasm, accounts for 1% of all bone tumors. It is encountered in any skeletal bones mainly in persons aged 10 and 25 years. Morphologically, it is represented as large homogenous cells--well-defined oval polygonal chondroblasts with a fine eosinophilic cytoplasm, and a round-to-oval nucleus. Cartilaginous portions of chondroblastoma form lobular structures. The tumor always comprises single-to-multiple multinucleate giant cells. The pathognomonic sign of chondroblastoma is intercellular reticular basophilically stained calcifications as a mesh. Mitotic cells, rather than abnormal ones, are present. There are cases of primary malignant chondroblastomas.

[Chondrosarcoma of the larynx].

Patients with chondrosarcoma of the larynx are diagnosed at the III-IV stages. Nevertheless, they have a relatively good prognosis. The tumor grows lowly, metastases develop late.

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer.

BACKGROUND: Abraxane (ABI-007) is a novel 130-nm, albumin-bound (nab) particle form of paclitaxel designed to utilize endogenous albumin pathways to increase intratumor concentrations of the active drug. This multicenter phase II study was designed to evaluate the efficacy and safety of Abraxane 260 mg/m2 every 3 weeks in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with histologically confirmed, measurable NSCLC received Abraxane as first-line therapy. RESULTS: Forty-three patients were enrolled. The overall response rate was 16%; the disease control rate was 49%. Median time to progression was 6 months, and median survival was 11 months. The probability of not having progressed by 1 year was 13%; the probability of surviving 1 year was 45%. No severe hypersensitivity reactions were reported despite the lack of premedication; 95% of patients were treated without dose reduction. Two patients (5%) discontinued therapy because of treatment-related toxicities (neuropathy, fatigue [1 each]). No grade 4 treatment-related toxicity occurred. CONCLUSIONS: Abraxane 260 mg/m2 administered IV over 30 min without premedication was well tolerated. Significant tumor responses and prolonged disease control were documented in this group of patients with NSCLC. Exploration of higher doses of ABI-007 alone and in combination with other drugs active in NSCLC is warranted.

[Ossifying fibromyxoid tumor].

Ossifying fibromyxoid tumor (OFMT) is a rare tumor of unknown histogenesis. It consists of chains and trabecules of ovoid cells in the fibromyxoid stroma (ICD code 8842/0). Tumor is frequently surrounded in part by a capsule of laminar bone. It is more frequent in males 14-79 years of age, mean 44 years. Soft tissues of extremities is a preferable location, but body, neck, oral cavity, mediastinum and retroperitoneal tissue can also be the site of OFMT. More than 100 OFMT cases are reported abroad. It is frequently masked by other tumors of soft tissues. We describe 3 cases in our country: 2 in 65 and 66 year old females and in a 44 year old male. Lipoma and soft tissue sarcoma were suspected clinically. Fibroblasts were found cytologically before operation in one case. Diagnosis was established after total biopsy of the tumor. One of the females is under observation after the operation without recurrence during more than two years. Preoperative diagnosis is sometimes possible when characteristic osteoblastic foci are observed.

[Adamantinoma of long tubal bones].

Four cases of adamantinomas of the long tubular bones, ulna and femur among them which rarely occur in patients aged 18-64 years (one female) are reported. A late metastasis to the sacrum was observed in one case. Typical diagnostic errors are described. Electron microscopy data are provided. Immunohistochemistry helps in differential diagnosis of this tumor. Histology does not give too much for the prognosis, radical resection does not influence the incidence of recurrences and metastases. The surgeons should be warned against enucleation of the tumor.

Extralesional resection for tumours of the pelvic bones.

A retrospective analysis of 92 patients with tumours of the bony pelvis is presented. Limbsparing operations may be adequate or inadequate. Adequate operations are those in which the excision is extralesional and the function of the limb is preserved as far as possible. An operation is inadequate if either oncological principles are abandoned or if carried out with no regard for them, but function is preserved to a greater extent. The postoperative mortality in 92 patients was 1.2%. In 12, oncological principles were not fulfilled. Long term results were available in 78 patients: 42 are alive and free of disease after more than 5 years, 17 of them for more than 10 years and 2 for more than 25 years. One patient with recurrence and metastases to the lungs is alive after 12 years.

[A surgical method in the complex treatment of metastatic bone tumors]. / Khirurgicheskii metod v kompleksnoi terapii metastaticheskikh opukholei kostei.

The article deals with the results of operations applied in the system of complex treatment of 83 patients (86 operations) with metastases of malignant tumours in the skeletal bones. Fourteen patient had carcinoma of the lung, 23--carcinoma of the breast, 28--carcinoma of the kidney, 8--carcinoma of the thyroid gland, and 10 patients had other malignant tumors. Operative interventions in the form of resection of the articular end or total removal of a tubular bone with endoprosthesis in affection of a long tubular bone and its pathological fracture or the threat of such fracture were substantiated. In the presence of special indications, osteosynthesis of the pathological fracture or amputation (exarticulation) of the limb may be undertaken. Laminectomy is indicated in metastatic lesion of the spine with the development of neurological disorders. Four (5%) patients died in the postoperative period. Average survival in the group of patients was 35 months, in the separate groups it was as follows: lung carcinoma metastases--9 months, kidney carcinoma metastases--31 months, thyroid carcinoma metastases--37 months, breast carcinoma metastases--40 months, metastases of other forms of malignant tumors--30 months. Longest survival--7.5 years. Average value of life quality according to Karnovsky was 30% before operation and 67% after it.

[Operations by the Bogoraz and Tikhov-Linberg methods as adequate interventions in malignant tumors of the extremities]. / Operatsii po Bogorazu i Tikhovu-Linbergu kak adekvatnye vmesha- tel'stva pri zlokachestvennykh opukholiakh konechnostei.

The author's conception on adequate operations is set forth. He considers adequate only those operations which are performed radically with abidance by ablastemic rules and consideration of the principle of a sheath structure and location after A. I. Rakov, with maintenance of the function of the operated on limb to a maximum degree. Both resection and amputation may be adequate as well as inadequate. The principle elaborated by N. A. Bogoraz and P. I. Tikhov underlies adequate resections. The author's data on the late-term results (follow-up periods of over 20 years) of resections after Tikhov-Linberg in malignant tumors of the ++brachio-scapular region are presented.

[Radical organ-saving operations in scapular tumors]. / O radikal'nykh sokhrannykh operatsiiakh pri opukholiakh lopatki.

The paper deals with analysis of data on 37 cases of scapular neoplasms who had undergone such radical function--saving surgery as interscapular-thoracic resection ( Tikhov - Linberg 's operation) (27) or scapulectomy (10). Modifications of both procedures developed by the authors are described. Their application was followed by an improved functional status as compared with other surgical procedures. Oncological status of 30 cases of primary scapular malignancies is discussed: 23 patients were recurrence- and metastasis-free during a follow-up period of 10 months-18 years (21 patients were operated on more than 5 years ago).

[Surgical treatment of metastatic lesions of the long tubular bones]. / Khirurgicheskoe lechenie bol'nykh s metastaticheskim porazheniem dlinnykh trubchatykh kostei.

The results of surgical treatment of 12 patients with metastases in long tubular bones are presented. Palliative surgery-reaction of the heads of bones or removal of the entire long tubular bone with prosthetic replacement--was performed in all cases. All the patients went through the operation well and were discharged from hospital. Pain subsided in all cases and the patients make satisfactory use of the operated extremities. The average survival time by the data of this report was 10.6 months. No local recurrences after bone resections were registered. Due to palliative surgery for metastases into long tubular bones, the patients do not suffer from pain, are mobile and self dependent again. A long survival time may be expected in some cases (solitary metastases), when such palliative procedures are employed.