Krebswissenschaft und -therapie

Primary ovarian carcinoid tumors are very rare, they represent less than 0.1% of all ovarian cancers. The insular type is the most common, followed by the stromal, trabecular and mucinous types. A woman of 47 years old presented with lower abdominal pain, ultrasound evaluation revealed a voluminous pelvic mass on the right side. The patient underwent debulking surgery, it was diagnosed a carcinoid of the left ovary with prevalent trabecular and partly cribriform and insular pattern. Our patient had periaortic lymph node metastases, in this respect there is no evidence of involvement of lymph nodes for primary ovary, especially in the trabecular form, except for intestinal and pulmonary carcinoids. Therefore, this is the fi rst case of mixed primary ovarian carcinoid, particularly in predominantly trabecular form, with lymph node metastases, as described in the literature.

Metastasis is the final result of actions of various genes, one of which is the Metastasis Associated 1 (MTA1) gene. MTA1 acts as part of a nucleosome remodeling and histone deacetylation complex and has been shown to aid metastasis by regulating many other molecules. We decided to study if there was any possible relationship between MTA1 and the phosphatase and tensin analogue mutated on chromosome 10 (PTEN). PTEN is a tumour suppressor gene known to be mutated in several cancers. We found that on knockdown of MTA1 using siRNA, PTEN protein levels increased albeit its mRNA levels were unchanged. We further found that MTA1 and PTEN colocalize and coimmunoprecipitate with each other. PTEN levels increased on inhibiting histone deacetyalse activity, such as possessed by MTA1. One of the most celebrated functions of PTEN is its regulation of the PI3K-Akt pathway. We found that the levels of active AKT decreased in cells treated with siRNA against MTA1. We hypothesize that MTA1 helps in maintaining the AKT pathway in cancer cells by inhibiting PTEN, a major antagonist of the pathway. This might be one of the several mechanisms by which MTA1 aids metastasis.

Glioblastoma is the most malignant brain tumor of astroglial origin. It renders poor response or resistance to existing therapeutics. We used all-trans retinoic acid (ATRA) and interferon gamma (IFN-?) alone and in combination for controlling human glioblastoma T98G xenograft in nude mice. Histopathological examination showed astrocytic differentiation in ATRA group, some apoptosis in IFN-? group, and occurrence of differentiation and enhancement of apoptosis in ATRA plus IFN-? group. ATRA plus IFN-? induced extrinsic pathway of apoptosis by activation of caspase-8 and cleavage of Bid to tBid and also promoted intrinsic pathway of apoptosis due to down regulation of hTERT, c-IAP2, and survivin and upregulation of Smac/Diablo. Mitochondrial release of apoptosis-inducing factor (AIF) induced caspase-independent pathway and also upregulation of calpain and caspase-dependent pathways ultimately activated caspase-3 for apoptosis. Increased activities of calpain and caspase-3 degraded 270 kDa ?-spectrin at the specific sites to generate 145 kDa spectrin breakdown product (SBDP) and 120 kD SBDP, respectively. In situ TUNEL and double immunofluorescent labelings detected apoptosis with increased expression of calpain, caspase-12, caspase-3, and AIF in tumors after treatment with IFN-? and most effectively with ATRA plus IFN-?. Results indicated that ATRA plus IFN-? activated multiple molecular mechanisms for increasing apoptosis in human glioblastoma in vivo.

The cancer stem cell theory proposes that there is a small but constant subpopulation of cancer cells with stem cell properties responsible for the self renewal capacity and unlimited proliferation of tumor as well as increased resistance to antineoplastic drugs. Targeting these cells might constitute an effective way to cure cancer. Regarding gliomas, by analysing proliferation kinetics of cultures containing mixed subpopulations and experimental data from literature on glioma cell lines, we propose a model (Stemness Phenotype Model) in which all glioma cells have stem cells properties but their phenotype varies depending on the environmental conditions. This model provides an alternative explanation to different and sometimes controversial experimental findings and might be a useful guide for future research in the field of gliomas and stem cell biology.

Purpose: To evaluate the relation between tumor size/volume, tumor range of motion, and healthy lung volume in light of radiotherapy motion management paradigm. Materials and Methods: Four patient data sets were considered in this investigation. Each patient underwent time resolved (4D) CT data scan. Mid-ventilation CT data sets, with nominal lung volumes ranging from ~3000 cm3 to ~6000 cm3, were considered for treatment planning. Spheres with pre-specified radii were auto-contoured in the left lower lobes as simulated planning target volumes (PTVs) for each patient. Motion in superior-inferior direction was superimposed on the simulated spherical PTVs, such that motion-inclusive ITVs were generated. Nine-field IMRT treatment plans were created for all lung volumes, different combinations of simulated PTV spherical size and ranges of motion. Three dose levels of 60 Gy, 70 Gy, and 80 Gy were utilized. The doses were prescribed to 95% of the ITV. Simulated PTV sizes and ranges of motion were varied until prescriptions were met, given that organs at risk (OARs) were spared. The OAR constraints were: 40 Gy to 1% of the cord and 30% of the heart, as well as 20 Gy and 30 Gy to 30% and 20% of benign lung, respectively. These constraints, representative for 2 Gy per fraction fractionation schemes, are commonly used clinically. The treatment plans were deemed clinically acceptable when standard deviation of the dose across the ITV was less than 3% of the prescription dose in addition to fulfillment of the OAR constraints. Results: For each nominal lung volume three look-up curves, corresponding to the prescription dose levels were generated. The plots related the PTV sphere sizes with its range of motion. In addition, correlation between the absolute tumor volume and its range of motion was also established and presented in graphical format. Conclusions: The motion management threshold of 0.5 cm found in the literature is reasonable. However, in some cases, depending on the tumor size, tumor range of motion, and nominal lung volumes, it might be too restrictive. In the determination of the most appropriate individualized treatment planning approach all factors such as tumor and lung volumes, tumor range of motion and patient tolerance toward the treatment technique need to be assessed.

Prostate cancer (PC) is the second leading cause of cancer deaths in men in America and Western Europe. Epidemiological studies suggest that prostate cancer incidence increased in last few years in Asian population. The causes or consequences of increasing trend of prostate cancer incidence are not completely known. Emerging evidences suggest that among the many risk factors, inflammation is the major risk factor for developing prostate cancer and its progression to metastasis. It is proposed that exposure to environmental factors such as infectious agents, dietary agents and saturated lipids leads to injury of the prostate due to chronic inflammation and regenerative risk factor lesions referred to as proliferative inflammatory atrophy (PIA). These phenomena predominantly control by a number of proinflammatory macro molecules such as chemokines, and their receptors. Some recent studies suggest that many of these pro-inflammatory chemokines and their receptors are the products of protooncogenes or tumor suppressor pathways in many cancers including that of the prostate. This review article will focus on the current biology of chemokines and chemokine receptors pathways in genesis of prostate cancer. An understanding of this axis may enable researchers to develop targeted strategies for prostate cancer.

Squamous cell carcinoma of the renal pelvis and ureter is a rare malignancy, having an incidence of 6% to 15% (of all urothelial tumors). Few cases of primary squamous cell carcinoma of kidney have been reported in the world literature. The insidious onset of symptom and lack of any pathognomonic sign, leads to delay in the diagnosis and subsequent treatment, resulting in grave prognosis for these patients. Herein, we report 5 cases (three males and two females) of advanced primary squamous cell carcinoma of kidney that were treated at our centre during the last 6 years. The average age was 57 years (range 50-65 years). Three of the patients had history of long standing renal calculus disease while 3 had history of smoking and 1 patient had history of analgesic abuse. These cases were unique because in few of them; all the calyces were involved by the tumor - a field change type of pattern normally seen in transitional cell carcinoma of the kidney. In one patient, thrombus of the inferior vena cava was also present along with infi ltration of the duodenum by the tumor. Despite prompt nephroureterectomy, 4 out of 5 patients died within 6 months of treatment. Only one patient was surviving at 5 months of follow up. Nephrectomy with or without ureterectomy is the treatment of choice in patients suffering from squamous cell carcinoma of the kidney. There is lack of evidence of survival benefi ts of chemo-radiation following surgery but is advocated by some with the hope that it might increase survival. Biopsy from the renal pelvis or calyceal wall is advocated at the time of stone removal in patients having long-standing history of large renal calculi or staghorn calculus since such patients are capable of harboring occult or overt malignancy.