Extent Of Tumor Growth Research Articles

Galectin-3 inhibition with belapectin combined with anti-OX40 therapy reprograms the tumor microenvironment to favor anti-tumor immunity

ABSTRACT Treatment with an agonist anti-OX40 antibody (aOX40) boosts anti-tumor immunity by providing costimulation and driving effector T cell responses. However, tumor-induced immune suppression contributes significantly to poor response rates to aOX40 therapy, thus combining aOX40 with other agents that relieve tumor-mediated immune suppression may significantly improve outcomes. Once such target is galectin-3 (Gal-3), which drives tumor-induced immunosuppression by increasing macrophage infiltration and M2 polarization, restricting TCR signaling, and inducing T cell apoptosis. A wide-variety of tumors also upregulate Gal-3, which is associated with poor prognosis. Tumor-bearing (MCA-205 sarcoma, 4T1 mammary carcinoma, TRAMP-C1 prostate adenocarcinoma) mice were treated with a Gal-3 inhibitor (belapectin; GR-MD-02), aOX40, or combination therapy and the extent of tumor growth was determined. The phenotype and function of tumor-infiltrating lymphocytes was determined by flow cytometry, multiplex cytokine assay, and multiplex immunohistochemistry. Gal-3 inhibition synergized with aOX40 to promote tumor regression and increase survival. Specifically, aOX40/belapectin therapy significantly improved survival of tumor-bearing mice through a CD8+ T cell-dependent mechanism. Combination aOX40/belapectin therapy enhanced CD8+ T cell density within the tumor and reduced the frequency and proliferation of regulatory Foxp3+CD4+ T cells. Further, aOX40/belapectin therapy significantly reduced monocytic MDSC (M-MDSCs) and MHC-IIhi macrophage populations, both of which displayed reduced arginase 1 and increased iNOS. Combination aOX40/belapectin therapy alleviated M-MDSC-specific functional suppression compared to M-MDSCs isolated from untreated tumors. Our data suggests that Gal-3 inhibition plus aOX40 therapy reduces M-MDSC-meditated immune suppression thereby increasing CD8+ T cell recruitment leading to increased tumor regression and survival.

The various evaluation of liver function focused on the major hepatectomy: a narrative review

: From long ago, hepatic fibrosis was known as the factor for unfavorable liver function. Most cases with hepatocellular carcinoma (HCC) have fibrosis to varying degrees among even the patients with Child-Pugh A. The severity of hepatic fibrosis is classified several stages, finally these resulted in the cirrhosis. Liver surgery for these patients showed a significantly increased mortality and morbidity. Besides, the patients with hepatic steatosis were increasing worldwide, these were 20% to 30% of peoples in the general population, meanwhile, 74% of obese peoples. Hepatic steatosis increases ischemia reperfusion injury and the risk of postoperative morbidity or mortality after liver surgery. Moreover, it was reported that the steatosis is correlated with liver functions, glucolipid metabolism and inflammation level among the patients with chronic hepatitis B. These pathological mechanism lead to impaired liver function. The complete resection of malignant hepatobiliary tumors is crucial for achieving long-term survival. Major hepatectomy is frequently required for complete resection, and main causes of unresectability is deficiency of remnant liver volume (RLV) or liver functional reserve (LFR). The complete resection of malignant hepatobiliary tumors is crucial for achieving long-term survival. Major hepatectomy is frequently required for complete resection, and main causes of unresectability is deficiency of RLV or LFR. Thus, while we perform major hepatectomy, the balance between the extent of hepatectomy considering the extent of tumor growth (tumor diameter, number, invasion into vessels) and LFR is especially important. This review article will highlight some of the current evaluations of LFR.

CD200 mimetic aptamer PEG-M49 markedly increases the therapeutic effects of pegylated liposomal doxorubicin in a mouse model of metastatic breast carcinoma: an effect independent of CD200 receptor 1.

We previously reported that CD200 overexpression in the host decreases progression and metastasis of the highly aggressive metastatic 4THM breast carcinoma. We have explored a possible synergistic interaction between the CD200 mimetic PEG-M49 and pegylated liposomal doxorubicin (Peg-Dox) in wild-type CD200 knockout (CD200-/-) and CD200 Receptor 1 knockout (CD200R1-/-) mice for the first time. A 4THM breast carcinoma model and three groups of BALB/c mice (wild type, CD200-/- and CD200R1-/-) were used. Five days after injection of tumor cells, mice were injected with Peg-Dox (ip, once a week) and PEG-M49 or a control aptamer (iv, every 3days). Necropsies were performed either 12 (mid-point) or 24 (endpoint) days after injection and the extent of tumor growth, visceral metastasis and changes in the tumor-directed immune response were evaluated. PEG-M49 and Peg-Dox co-treatment induced complete tumor regression and loss of macroscopic lung metastasis in four out of seven WT mice. This synergistic anti-tumoral effect is thought to be due to Peg-M49-induced inhibition of Gr1 + CD11b + cells and Peg-Dox-induced increases in tumor-infiltrating CD8 + and CD8CD4 double-positive cells. Similar changes were observed in CD200R1-/- mice indicating that the primary effects of Peg-M49 are mediated by non-CD200R1 receptors. We also demonstrated for the first time that tumor growth, metastasis, and tumor infiltrating GR1 + CD11b + cells were markedly increased in CD200R1-/- mice, indicating an anti-inflammatory and protective role of CD200. CD200 mimetics might be a safe and effective immunomodulatory treatment in conjunction with classical chemotherapeutics for therapy of aggressive metastatic breast carcinoma.

Pathological-anatomical diagnosis according to the German lung cancer guideline 2018

The German S3-guideline on prevention, diagnosis, therapy and follow-up of lung cancer, published in February 2018, expands on the 2010 guideline to include atotal of 19recommendations and statements regarding the "processing of lung resection specimens (tumor resection specimens)", "processing of lymph nodes", "histo-pathological typing and immunophenotype", "extent of tumor growth in resection specimens", "resection margins" or "R-classification", "grade of malignancy (grading)", "regression grading" as well as the "examination of molecular targets". The statements regarding the analysis of molecular targets result from the diagnostic requirements of the current targeted therapy of advanced lung cancer. At the same time, apathological-anatomical diagnosis according to the current S3-guideline fulfills all corresponding requirements in certified lung cancer centers.

Facial Nerve Function after Microsurgical Removal of the Vestibular Schwannoma

Technological development in microsurgery during the 20th century has led to a significant decline in mortality and morbidity of the surgical management of vestibular schwannoma. Postoperative facial nerve function belongs among the main criteria of success. Retrospective analysis focused on 90 patients undergoing retrosigmoid - transmeatal surgery of vestibular schwannoma during the period of 2010 – 2012. The aim of the study was to evaluate perioperative factors, associated with postoperative facial nerve function. Facial nerve was discontinuous in nine cases (10 %) that were subsequently reconstructed. Position of the facial nerve to the tumor, morphological changes (e.g. elongation and splaying), cystic component of tumor and extent of tumor growth into the fundus of internal acoustic meatus were among the parameters affecting facial nerve preservation. Definitive excellent to good function (House - Brackmann grade1 to 3) was achieved in 96 % of patients in the group with preserved facial nerve continuity. In the group with facial nerve reconstruction there were 67 % of patients with good definitive postoperative function. Stimulation threshold at the end of the surgery brought no significant information about definitive function of the facial nerve, however it predicted early postoperative outcome. Currently it is possible to preserve the facial nerve continuity in the vast majority of surgically managed vestibular schwannomas cases. It is crucial to define prognostic factors influencing the facial nerve injury, and include them into the decision making protocol. For the same reason it is necessary to define factors, which lead to unfavorable outcomes of the facial nerve function despite its anatomical preservation.

Which factors affect the long-term survival of patients with hepatocellular carcinoma UICC stage IV?

In the 7th edition of the TNM classification, not only HCC with distant metastases but also those with regional lymph node metastases are classified as stage IV. From our prospectively recorded tumor registry, 138 patients (17%) with HCC were in stage IV. Among those were 68 and 70, respectively, in stage IVA (regional lymph node metastases) and IVB (distant metastases). The tumors were less frequently treated with resection or local ablative treatment (chemoembolization, RFA, SIRT, percutaneous radiation) than patients in stage I-III. Ten HCCs were resected. Five of the resected patients were in stage IVA and five in stage IVB. After tumor resection, patients lived longer than those who underwent local or systemic treatment only (p=0.003 or p=0.001, respectively). In the univariate survival analysis, the stage IV patients' long-term survival was decreased statistically significantly through elevated bilirubin, low albumin, Okuda stage III and BCLC stage D. Patients' age and sex, pre-treatment AFP level, Child stage and the presence of venous invasion did not influence survival. In the multivariate analysis (Cox regression), tumor resection and BCLC stage were independent prognostic factors. Patients with HCC in TNM stage IV have a very poor prognosis. Only few patients are eligible for resection because of the extent of tumor growth, comorbidities and general condition. These, however, benefit markedly from tumor resection with lymph node dissection and possibly resection of distant metastases.

Diagnosis of Cancer of the Left Colon, Complicated by Acute Intestinal Obstruction

Between 2003 and 2012 in the Alexandrovskaya Hospital of St. Petersburg, Russia 2200 patients were hospitalized with cancer of the left colon complicated by acute intestinal obstruction, ageing from 26 to 91 years. 44.2% were men, 55.8% were women. Th e subjects of the study were 1019 patients in whom distant metastases had not been identifi ed. Th is study is an analysis of the role of physical, laboratory and instrumental methods of examining patients with acute intestinal obstruction due to cancer of left colon. Conclusions: 1. Up to 80% of patients were admitted to hospital aft er 48 hours from onset of the acute period of the disease, aff ecting the variability of clinical manifestations in acute intestinal obstruction due to cancer of left colon. 2. From instrumental methods, the most informative is X-ray examination. When ultrasound is characterized by a tensile intestinal loops. 3. Fibrocolonoscopy, with eff ectively implementation, allows for a 100% positive diagnosis, but only 13.7% of subjects go on to therapeutic manipulation. 4. Laparoscopy avoids a long-term observation of the passage of barium sulfate in patients with suspected acute intestinal obstruction and is the most eff ective way to determine the cause of intestinal obstruction in a complex of diagnostic measures. It is an eff ective diagnostic tool for fi rst-stage or fi nal stage in the treatment of intestinal obstruction. 5. Computed tomography, having a sensitivity of 97.4% is the preferred method of detecting metastases to determine the source and extent of tumour growth which certainly can and should infl uence the decision as to adopt a surgical approach. Refs 10. Tables 9.

Operative Versorgung V.-cava-inferior-assoziierter urologischer Tumorerkrankungen

Tumor lesions of the inferior vena cava are extremely challenging with regard to adequate therapeutic management also in advanced malignant urological tumor lesions which can be caused by malignant adhesion, impression and tumor infiltration from the surrounding tissue. This can be the case with metastases from a seminoma or testicular carcinoma (differential diagnosis: primary vena cava leiomyosarcoma), tumor-associated growth into and within the inferior vena cava originating from renal cell carcinoma or carcinoma of the pararenal gland. The aim of this overview was to summarize current clinical and operative experiences in the treatment of inferior vena cava-associated urological tumor lesions, perioperative management, individual-specific and finding-adapted surgical technique and possible outcome, including prognostic considerations from clinical daily practice and representative data found in the literature. The primary aim of the surgical approach is to achieve R0 resection with reconstruction of the inferior vena cava lumen providing a reasonable risk-benefit ratio, which comprises i) complete resection and substitution of the inferior vena cava by a prosthesis along the previous extent of tumor growth, ii) partial resection of the vena cava wall with subsequent patch-plasty or tangential resection with primary suture or iii) removal of the vena cava thrombus after cavotomy. Particular attention should be paid to tumor thrombi reaching the right atrium which need to be extracted after sternotomy and atriotomy using an extracorporeal circulation (cardiac surgeon). For surgical planning, subdivision of the inferior vena cava into three segments, infracardiac, infrahepatic and infrarenal third, has been proven and tested. The current development status and advances in surgical approaches as well as advances in medical technology allow the successful approach to such advanced stage urological tumor manifestations. A deciding factor is the abdominal and cardiovascular surgical expertise of each surgeon after formation of a team of surgical specialists (including urologists) and only then prognostic advantages can be achieved.

Abstract 2825: Using SHG to study breast cancer tumor progression.

Abstract The majority of cancer mortality is a result of metastatic events, making it increasingly important to uncover prognostic markers that can predict the metastatic potential of a primary tumor to aid in determining the best course of patient treatment. Stromal extracellular matrix restructuring increases efficiency of cell migration away from the primary tumor into surrounding tissues and vasculature, thereby enhancing metastatic potential. We have determined that the ratio of the forward propagating to backward propagating Second Harmonic Generation (SHG) signals from type I collagen can be used as a quantitative method of differentiating healthy and tumor breast tissue, and tracking stromal changes throughout tumor progression. Tumors were graded and staged according to standard pathological qualifications, incorporating morphological changes in the tissue as well as extent of tumor growth and invasion. As the tumor cells initiate development in the ducts of the breast tissue the F/B ratio of the fibrillar collagen does not change. Upon progression from an in situ to an invasive carcinoma the F/B ratio of ductal tumors significantly decreases. Taking a closer look at this phenomenon, to examine whether the invasion through the basement membrane into the surrounding tissue causes an immediate change in the F/B ratio, tumors of varying grade and stage were analyzed showing significant trends throughout development. Increased tumor grade was associated with a gradual decrease in the F/B ratio, whereas size of the tumor had no significant effect on the F/B but all sizes were significantly lower than healthy tissue. Interestingly, there was a significant increase in the F/B ratio associated with the furthest progression of lymph-node involvement. Invasive Lobular Carcinoma analysis revealed a similar decrease in F/B, but was not affected by lymph node involvement. On the other hand F/B of these tumors was significantly affected by an interaction with the chest or skin. These results provide insight into the different development processes undergone by two related breast carcinomas, which could differ due to their alternative methods of invasion and stromal components. F/B ratio measurements can be used alongside pathological analysis to provide information about the metastatic potential of the primary tumor, as demonstrated by the relationship between F/B ratio of IDC and lymph node metastasis. Enhanced scientific understanding of stromal development could be applied to the development of improved biomarkers and metastatic treatment methods. Citation Format: Kathleen A. Burke, Edward Brown. Using SHG to study breast cancer tumor progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2825. doi:10.1158/1538-7445.AM2013-2825

A novel murine model of human renal cell carcinoma spinal metastasis

There is currently no reproducible animal model of renal cell carcinoma (RCC) spinal metastasis that allows for laboratory study of the human disease. In this report, we describe an animal model that reliably reproduces RCC spinal metastasis using a human tumor cell line. A posterior surgical approach was used to implant tumor cells into the lamina of immunosuppressed mice. Histology sections were analyzed 12weeks after tumor cell implantation to quantify the location and extent of tumor growth. RCC xenografts grew in treated animals (8 mice) with a reproducible pattern of growth. After implantation, tumor growth occurred primarily in the antero-posterior dimension. At 8weeks after tumor cell implantation, there was visible tumor growth in all treated mice. Histologic correlation at 12weeks after tumor cell implantation confirmed tumor growth involving primarily the paraspinal region and lamina. Our investigation resulted in an orthotopic model of human RCC spinal metastasis. Ultimately this will allow testing of targeted therapies for RCC with spinal involvement. Furthermore, this model can be expanded to develop similar spinal metastasis models for other tumor cell lines.

Pediatric Sinonasal Inverted Papilloma: An Uncommon Occurrence and Its Proposed Management

Inverted papilloma (IP) represents 0.4 to 4.7% of polypoid lesions of the nose and paranasal sinuses. It characteristically presents in the 5th to 6th decade of life, with a 3:1 male predilection. IP most commonly arises along the lateral nasal wall or occasionally from the maxillary antrum or sinus.1,2 Although characterized as a benign tumor, it demonstrates a high recurrence rate and has the capacity to expand by local extension into vital structures.3 Concurrent squamous cell carcinoma (SCC) has been found in 3-10% of cases.3,4 The etiology of IP is unclear, but human papillomavirus (HPV) and Epstein-Barr Virus (EBV), have been implicated in its development.1,2,4 Endoscopic exam reveals a papillomatous, polypoid mass which can fill the entire nasal cavity, often involving more than one sinus, making the point of attachment difficult to identify in the awake patient. CT imaging may delineate the origin at a point of bony sclerosis or deformation of the nasal wall, whereas MRI helps distinguish the mass from inspissated secretions or inflammatory changes, and allows evaluation of the extent of tumor growth.2 Pathologic examination is necessary to distinguish IP from other polypoid lesions of the sinonasal tract. It is histologically characterized by hyperplastic ribbons of squamous or ciliated columnar multilayered epithelium mixed with mucocytes that grows endophytically into the underlying stroma.1,4 IP has rarely been described in the pediatric patient population, with less than 20 confirmed cases in the English language literature. Hyam’s landmark study of 149 patients with sinonasal IP included no pediatric cases.5 Schramm’s series of 376 pediatric nasal masses did not include a single case of IP.6 Pediatric Sinonasal Inverted Papilloma: An Uncommon Occurrence and Its Proposed Management Benjamin Y. Rafii, MD1,3; Maggie A. Kuhn, MD1,3; Elana Opher, MD4; Aaron Hartman, MD4; and Jessica W. Lim, MD2,3 Department of Otolaryngology, 1NYU School of Medicine and 2SUNY Downstate, Departments of 3Otolaryngology and 4Pathology, Lenox Hill Hospital

Defining the Clinical Target Volume for Bladder Cancer Radiotherapy Treatment Planning

There are currently no data for the expansion margin required to define the clinical target volume (CTV) around bladder tumors. This information is particularly relevant when perivesical soft tissue changes are seen on the planning scan. While this appearance may reflect extravesical extension (EVE), it may also be an artifact of previous transurethral resection (TUR). Eighty patients with muscle-invasive bladder cancer who had undergone radical cystectomy were studied. All patients underwent preoperative TUR and staging computed tomography (CT) scans. The presence and extent of tumor growth beyond the outer bladder wall was measured radiologically and histopathologically. Forty one (51%) patients had histologically confirmed tumor extension into perivesical fat. The median and mean extensions beyond the outer bladder wall were 1.7 and 3.1 mm, respectively. Thirty five (44%) patients had EVE, as seen on CT scans. The sensitivity and specificity of CT scans for EVE were 56% and 79%, respectively. False-positive results were infrequent and not affected by either the timing or the amount of tissue resected at TUR. CT scans consistently tended to overestimate the extent of EVE. Tumor size and the presence of either lymphovascular invasion or squamoid differentiation predict a greater extent of EVE. In patients with radiological evidence of extravesical disease, the CTV should comprise the outer bladder wall plus a 10-mm margin. In patients with no evidence of extravesical disease on CT scans, the CTV should be restricted to the outer bladder wall plus a 6-mm margin. These recommendations would encompass microscopic disease extension in 90% of cases.

The anticancer activity of the transcription inhibitor terameprocol (meso-tetra-O-methyl nordihydroguaiaretic acid) formulated for systemic administration

Terameprocol (meso-tetra-O-methyl nordihydroguaiaretic acid, formerly known as EM-1421 and M4N) is a semi-synthetic small molecule with antitumor activity occurring via selective targeting of Sp1-regulated proteins, including survivin and cdc2 that control cell cycle and apoptosis. Terameprocol is in clinical development as a site-specific transcription inhibitor in solid refractory tumors. The present studies were designed to investigate the in-vitro and in-vivo anticancer activity of terameprocol in a novel hydroxypropyl beta-cyclodextrin and polyethylene glycol solvent formulation (designated CPE) designed for safe parenteral administration. Terameprocol powder was dissolved in CPE (20% hydroxypropyl beta-cyclodextrin and 50% polyethylene glycol 300 or 30% hydroxypropyl beta-cyclodextrin and 25% polyethylene glycol 300) or dimethyl sulfoxide and used for in-vitro cell proliferation assays, and in human carcinoma xenograft studies using female athymic nude mice injected with SW-780 human bladder cells. Terameprocol (50 and 100 mg/kg), paclitaxel (5 mg/kg), terameprocol and paclitaxel or vehicle was administered intraperitoneally daily for 21 days. Stock solutions of the CPE formulation were stable for up to 12 months. Terameprocol CPE formulation showed concentration-dependent inhibition of HeLa and C33A cell proliferation, and was less toxic than terameprocol dimethyl sulfoxide formulation. The terameprocol CPE formulation showed no overt toxicities in tumor-bearing mice. Terameprocol alone reduced the rate of tumor growth, and a combination of terameprocol/paclitaxel reduced both the rate and extent of tumor growth. These preclinical results confirm the tumoricidal activity of terameprocol formulated in a solvent suitable for parenteral administration and suggest that terameprocol has improved efficacy when coadministered with paclitaxel.

Expression of Leptin, Leptin Receptor, and Hypoxia‐Inducible Factor 1α in Human Endometrial Cancer

Recent studies suggested that Ob (Ob) and its receptor (ObR) could be involved in the pathogenesis of various human malignancies, among others in endometrial cancer. Moreover, hypoxia, which is associated with solid tumors, might stimulate, through hypoxia-inducible factor 1alpha (HIF-1alpha), expression of Ob and ObR. In this article, we analyzed by immunohistochemistry the expression of Ob, ObR, and HIF-1alpha in 60 cases of human endometrial cancer tissues as well as in 25 cases of normal endometria. Additionally, we assessed correlations among studied proteins as well as relationships with selected clinicopathological features of endometrial cancer. Immunoreactivity for Ob, ObR, and HIF-1alpha protein was observed in 56.7%, 30.0%, and 78.3% of endometrial cancers, respectively. The expression of HIF-1alpha showed a significant positive correlation with Ob (P < 0.0001, r = 0.573) and ObR (P = 0.020, r = 0.299). Moreover, we noted positive correlation between Ob and ObR (P = 0.001, r = 0.429). No statistically significant relationship was revealed between Ob, ObR, and HIF-1alpha protein in regard to patient's age, histological grade, and extent of tumor growth (pT). In conclusion, HIF-1alpha, which is related to tissue hypoxia in endometrial cancer, seems to be associated with overexpression of Ob and ObR. Ob could exert autocrine effect to stimulate endometrial cancer progression. Thus the autocrine Ob loop should be taken into consideration as a novel potential target in endometrial cancer prevention and treatment.

Insulin‐Like Growth Factor‐I Receptor Correlates with Connexin 26 and Bcl‐xL Expression in Human Colorectal Cancer

Insulin-like growth factor (IGF) and its receptor (IGF-IR) play an important role in mitogenesis, apoptosis, growth, and proliferation of several types of cancers. Overexpression of IGF-IR in colorectal cancer is associated with increase of cancer cell proliferation and migration as well as inhibition of apoptosis. In our previous reports we demonstrated correlations between IGF-IR and apoptosis. Moreover, we observed relationships between connexin26 (Cx26) expression and apoptotic markers in human colorectal cancer. Recently, it has been shown that expression of connexins and gap junction (GJ) functions are also regulated by growth factors, including IGF-I. Therefore, in this study we have focused on the relationships between IGF-IR and Cx26 as well as Bcl-xL expression. A total number of 115 cases of colorectal cancer were examined by immunohistochemistry, using the avidin-biotin-peroxidase method. Associations among the above proteins were assessed in the entire group of colorectal cancer patients and its subgroups, depending on lymph node involvement (N0 and N1), histological grade (G2 and G3), extent of tumor growth (pT1+pT2 and pT3+pT4), histopathologic type (adenocarcinoma and mucinous carcinoma), sex, age (<or=60 and>60), and tumor site (colon and rectum). The expression of IGF-IR, Cx26, and Bcl-xL was noted in 47%, 56.5%, and 75.6% of the tumors, respectively. In the entire group of patients we found a positive correlation between IGF-IR and Cx26 (P<0.0001, r=0.374) as well as between IGF-IR and Bcl-xL (P<0.0001, r=0.344). Our results may suggest that the insulin-like growth system is involved in regulation of apoptosis and probably connexin expression in colorectal cancer cells.

Levels of Ve-Cadherin Increase Independently of Vegf in Preoperative Sera of Patients with Colorectal Cancer

Vascular endothelial cadherin (VE-cadherin) preserves the tightness of the mature vascular network as a component of endothelial adherens junctions. Vascular endothelial growth factor (VEGF) makes VE-cadherin dissociate from complexes with beta-catenin, so that endothelial cells can loosely proliferate and migrate. We searched for relationships between VEGF and VE-cadherin levels in preoperative sera of patients with colorectal cancer (CRC). We also compared VE-cadherin levels of control and preoperative CRC sera in relation to clinicopathological features. We measured with an ELISA kit the serum levels of the proteins in preoperative samples from 125 CRC patients and in samples from 16 healthy volunteers. Serum VE-cadherin was about fourfold higher in CRC patients than in controls (P < 0.00001), with similar results being found in subgroups with different clinicopathological features versus controls. VE-cadherin was not correlated with VEGF in the entire group of CRC patients nor in the subgroups of node-positive and node-negative patients, different grades of histological differentiation (G2 or G3), extent of tumor growth (pT1+pT2 or pT3+pT4), histopathological type (adenocarcinoma or mucinous carcinoma), sex, age, and tumor site (colon or rectum). However, the serum levels of VE-cadherin and VEGF in CRC patients, which were higher than the mean values of controls, tended towards a negative correlation in node-positive patients (P = 0.078, r = -0.279). VEGF and VE-cadherin seem to be independent markers of angiogenesis in CRC with no significant correlation between their serum levels.

Relationships among tumor burden, tumor size, and the changing concentrations of fibrin degradation products and fibrinolytic factors in the pleural effusions of rabbits with VX2 lung tumors

The VX2 tumor is derived from a papilloma virus-induced rabbit epithelial cell line. If VX2 tumor cells (trapped in a plasma clot) are introduced intravenously into NZW rabbits, the cells lodge in the lung capillary bed and produce tumors. Independently of the tumor burden (ie, the total tumor weight per rabbit), approximately 15% of rabbits with VX2 lung tumors accumulate an effusion in the interpleural space and this pleural effusion contains products of hemostasis. We hypothesized that these products were of intra-tumoral origin and that they changed in concentration as tumor burden increased. Interrelationships among lung-, tumor-weights, and pleural effusion volumes, and the concentrations of fibrinolytic factors, their catabolic products, and other proteins of pleural effusions were measured in rabbits with a wide range of tumor burdens. Positive correlations between tumor burden and total lung weight and between pleural effusion volume and net lung weight suggested that interstitial fluid from the stroma of tumors passed directly into the extravascular space of the lung(s) and into the interpleural space(s). Analyses of pleural effusions indicated that plasminogen-, alpha(2)-antiplasmin-, and plasminogen activator inhibitor-1-related proteins, urokinase-like- and tissue-plasminogen activator activities, and vascular endothelial growth factor increased in concentration up to a tumor burden of approximately 20-25 g. Plasmin activity and intact fibrinogen were absent. The concentration of fibrin(ogen) degradation products did not change significantly up to a tumor burden of approximately 25 g but increased substantially as tumor burdens exceeded 25 g. In conclusion, interstitial fluid from tumors enters the extravascular space of the host and may accumulate with fluid from non-tumor sources as a pleural effusion. The concentrations of fibrinolytic factors and their products in pleural effusions reflect the tumor burden of the rabbit. Conceivably, the components of a malignant effusion contain much information about the extent of tumor growth.

A novel early-stage orthotopic model for ovarian cancer in the Fischer 344 rat

The purpose of our study was to ascertain the progression of metastases in a novel ovarian cancer model designed to mimic early-stage disease by utilizing an orthotopic injection technique. Female Fischer 344 rats were injected with either 10(4) or 10(5) NuTu-19 cells by intraperitoneal or orthotopic injection. Peritoneal washings and histologic specimens were examined to correlate the incidence and extent of tumor growth. In a second phase, orthotopic injections of 10(2) and 10(3) cells were compared to that of 10(4) cells. Progression of ovarian cancer was observed by gross and microscopic examinations in both intraperitoneal and orthotopic models. Pelvic extension and abdominal adhesions uniquely characterized the orthotopically injected animals. Numbers of identifiable metastases declined with lower cell inocula, confirming that early-stage disease was extended to at least 14 days with 10(2) NuTu-19 cells. The orthotopic ovarian cancer model emulates early disease with the initiation of a primary tumor that is localized within the inherent microenvironment. The orthotopic model offers a clinically relevant alternative for future cancer research that allows for the investigation of therapeutic strategies against early stages of the disease process.

A novel early-stage orthotopic model for ovarian cancer in the Fischer 344 rat

The purpose of our study was to ascertain the progression of metastases in a novel ovarian cancer model designed to mimic early-stage disease by utilizing an orthotopic injection technique. Female Fischer 344 rats were injected with either 104or 105NuTu-19 cells by intraperitoneal or orthotopic injection. Peritoneal washings and histologic specimens were examined to correlate the incidence and extent of tumor growth. In a second phase, orthotopic injections of 102and 103cells were compared to that of 104cells. Progression of ovarian cancer was observed by gross and microscopic examinations in both intraperitoneal and orthotopic models. Pelvic extension and abdominal adhesions uniquely characterized the orthotopically injected animals. Numbers of identifiable metastases declined with lower cell inocula, confirming that early-stage disease was extended to at least 14 days with 102NuTu-19 cells. The orthotopic ovarian cancer model emulates early disease with the initiation of a primary tumor that is localized within the inherent microenvironment. The orthotopic model offers a clinically relevant alternative for future cancer research that allows for the investigation of therapeutic strategies against early stages of the disease process.

Surgical treatment of renal cell carcinoma with intravascular extension

Long-term survival after surgical treatment is possible in patients with renal cell carcinoma (RCC) extending in the right atrium. Different surgical techniques for the treatment of patients with RCC extending into the vena cava have been advocated, depending on the proximal extent of the tumor. We present and propose an algorithm regarding the operative strategy depending on the extent of tumor growth.