Protein expression could guide NSCLC chemotherapy choice

Protein expression analysis is technically possible as a means of guiding chemotherapy decisions in patients with a new diagnosis of advanced non-small-cell lung cancer, US investigators say.

via Med Wire News

NSCLC immunization ‘proof of concept’ achieved

Immunization against MAGE-A3 is a feasible adjuvant treatment in patients with resectable non-small-cell lung cancer expressing the tumor-specific antigen, research suggests.

via Med Wire News

Young Black men least likely to undergo prostate cancer screening follow-up

Black men under the age of 65 years are significantly less likely to receive follow-up after an elevated prostate-specific antigen (PSA) test than White men, research shows.

via Med Wire News

Prostatectomy patients ‘should be spared bowel preparation’

Japanese research shows that patients with T1 or T2 prostate cancer who do not undergo mechanical bowel preparation prior to laparoscopic prostatectomy fair no worse than patients who do.

via Med Wire News

Signaling pathway switch in breast cancer

Next generation sequencing studies have drawn the general landscape of breast cancers and identified hundreds of new, actual therapeutic targets. Two major signaling pathways seem to be altered in a vast proportion of breast cancers. The PI3 kinase/AKT pathway is activated and the JUN/MAPK pathway is repressed. Via the regulation of the cell cycle this metabolic switch impacts on the balance between self-renewal, proliferation and differentiation of the tumor-initiating cells

via Cancer Cell International

L1cam promotes tumor progression and metastasis and is an independent unfavorable prognostic factor in gastric cancer

Background: Previous reports have demonstrated that L1cam is aberrantly expressed in various tumors. The potential role of L1cam in the progression and metastasis of gastric cancer is still not clear and needs exploring. Methods: Expression of L1cam was evaluated in gastric cancer tissues and cell lines by immunohistochemistry and Western blot. The relationship between L1cam expression and clinicopathological characteristics was analyzed. The effects of L1cam on cell proliferation, migration and invasion were investigated in gastric cancer cell lines both in vitro and in vivo. The impact of L1cam on PI3K/Akt pathway was also evaluated. Results: L1cam was overexpressed in gastric cancer tissues and cell lines. L1cam expression was correlated with aggressive tumor phenotype and poor overall survival in gastric cancer patients. Ectopic expression of L1cam in gastric cell lines significantly promoted cell proliferation, migration and invasion whereas knockdown of L1cam inhibited cell proliferation, migration and invasion in vitro as well as tumorigenesis and metastasis in vivo. The low level of phosphorylated Akt in HGC27 cells was up-regulated after ectopic expression of L1cam, whereas the high level of phosphorylated Akt in SGC7901 cells was suppressed by knockdown of L1cam. Moreover, the migration and invasion promoted by L1cam overexpression in gastric cancer cells could be abolished by either application of LY294002 (a phosphoinositide-3-kinase inhibitor) or knockdown of endogenous Akt by small interfering RNA. Conclusions: Our study demonstrated that L1cam, overexpressed in gastric cancer and associated with poor prognosis, plays an important role in the progression and metastasis of gastric cancer.

via Journal of Hematology & Oncology

Target delivery of MYCN siRNA by folate-nanoliposomes delivery system in a metastatic neuroblastoma model

Background: Folate-nanoliposomes delivery system has emerged recently as a specific and safety delivery method and gradually used as the carrier of a variety kinds of drugs including compounds, plasmids and siRNAs. Methods: In this study, we established a bone marrow and bone metastasis xenograft mouse model by injecting the LA-N-5 cell into the bone marrow cavity. Fluorescence microscopy, TUNEL Assay, Quantitative RT-PCR and western blot were conducted to analysis the distribution of folate-nanoliposomes entrapped MYCN (V-myc myelocytomatosis viral related oncogene) siRNA in mice and the relevant suppression effect. Results: The folate-nanoliposomes entrapped MYCN siRNA can be specifically distributed in tumor tissues. Further study shows that folate-nanoliposomes entrapped MYCN siRNA lead to MYCN mRNA expression significantly down-regulated (>50%, and p<0.05) compared with negative control siRNA treatment. MYCN protein expression was inhibited about 60% in vivo, thus induced tumor cell apoptosis markedly. Conclusion: This study point to a new way for treatment of metastatic neuroblastoma and could widen the application of folate-nanoliposomes delivery system in tumor therapy.

via Cancer Cell International

Curcumin induces apoptosis in gallbladder carcinoma cell line GBC-SD cells

Background: Gallbladder carcinoma is a malignant tumor with a very low 5-year survival rate because of the difficulty with its early diagnosis and the very poor prognosis of the advanced cancer state. The aims of this study were to determine whether curcumin could induce the apoptosis of a gallbladder carcinoma cell line, GBC-SD, and to clarify its related mechanism. Methods: First, the anti-proliferative activities of curcumin-treated and untreated GBC-SD cells were determined using the MTT and colony formation assays. Then, the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay and Hoechst 33342 staining assay. Detection of mitochondrial membrane potential was used to validate the ability of curcumin on inducing apoptosis in GBC-SD cells. Cell cycle changes were detected by flow cytometric analysis. Finally, the expressions of the apoptosis-related proteins or genes caspase-3, PARP, Bcl-2, and Bax were analyzed by western blot and quantitative real time PCR assay. Statistical analyses were performed using the Student's t-test for comparison of the results obtained from cells with or without curcumin treatment. Results: The MTT assay revealed that curcumin had induced a dose- and a time-dependent decrease in cell viability. Colony counting indicated that curcumin had induced a dose-dependent decrease in the colony formation ability in GBC-SD cells. Cells treated with curcumin were arrested at the S phase, according to the flow cytometric analysis. A significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. Morphological changes in apoptotic cells were also found by the Hoechst 33342 staining. After treatment with curcumin fluorescence shifted from red to green as DeltaPsim decreased. Furthermore, western blot and quantitative real time PCR assays demonstrated that the curcumin induced apoptosis in GBC-SD cells by regulating the ratio of Bcl-2/Bax and activating the expression of cleaved caspase-3. Conclusions: Taken together, the results indicate that curcumin may be a potential agent for the treatment of gallbladder cancer.

via Cancer Cell International

Exophytic RCC lesions predict benign histology

Age, gender, and exophytic properties may help clinicians predict benign histology in patients with T1a renal cell carcinomas, suggest findings published in the International Journal of Urology.

via Med Wire News

Poor evidence occludes locally advanced RCC surgery recommendations

Researchers have failed to find sufficient evidence to conclude whether concomitant lymph node dissection or ipsilateral adrenalectomy with radical nephrectomy improves oncologic outcomes for patients with locally advanced renal cell carcinoma.

via Med Wire News

Best sequence for optimal targeted mRCC therapy remains elusive

The use of targeted therapies for metastatic renal cell carcinoma could see patients surviving in excess of 2 years, suggest findings from the Institut Gustave Roussy in Paris, France.

via Med Wire News

Genistein promotes cell death of ethanol-stressed HeLa cells through the continuation of apoptosis or secondary necrosis

Background: Apoptosis is a major target and treatment effect of multiple chemotherapeutical agents in cancer. A soybean isoflavone, genistein, is a well-studied chemopreventive agent and has been reported to potentiate the anticancer effect of some chemotherapeutics. However, its mechanistic basis of chemo-enhancement effect remains to be fully elucidated. Methods: Apoptotic features of low concentration stressed cancer cells were studied by microscopic method, western blot, immunostaining and annexin V/PI assay. Genistein's effects on unstressed cells and recovering cells were investigated using MTT cell viability assay and LDH cytotoxicity assay. Quantitative real-time PCR was employed to analyze the possible gene targets involved in the recovery and genistein's effect. Results: Low-concentration ethanol stressed cancer cells showed apoptotic features and could recover after stress removal. In stressed cells, genistein at sub-toxic dosage promoted the cell death. Quantitative real-time PCR revealed the up-regulation of anti-apoptotic genes MDM2 and XIAP during the recovery process in HeLa cells, and genistein treatment suppressed their expression. The application of genistein, MDM2 inhibitor and XIAP inhibitor to the recovering HeLa cells caused persistent caspase activity and enhanced cell death. Flow cytometry study indicated that genistein treatment could lead to persistent phosphatidylserine (PS) externalization and necrotic events in the recovering HeLa cells. Caspase activity inhibition shifted the major effect of genistein to necrosis. Conclusions: These results suggested two possible mechanisms through which genistein promoted cell death in stressed cancer cells. Genistein could maintain the existing apoptotic signal to enhance apoptotic cell death. It could also disrupt the recovering process in caspase-independent manner, which lead to necrotic events. These effects may be related to the enhanced antitumor effect of chemotherapeutic drugs when they were combined with genistein.

via Cancer Cell International

Pathologic fracture does not influence prognosis in stage IIB osteosarcoma: a case--control study

ObjectiveThis study tested the implication of pathologic fractures on the prognosis in stage IIb osteosarcoma. Methods: A single center retrospective evaluation of clinical management and oncologic outcome was conducted with 15 pathological fracture patients (M:F = 10:5; age: mean 23.2, range 12--42) and 50 non-fracture patients between April 2002 and December 2010. These stage IIB osteosarcoma patients were matched for age, tumor site (femur, tibia, and humerus), and osteosarcoma subtype (i.e., control patients with osteosarcoma in the same sites as the fracture patients). All osteosarcoma patients with pathological fractures underwent brace or cast immobilization, adjuvant chemotherapy, and limb salvage surgery or amputation. Musculoskeletal Tumor Society (MSTS) functional scores were assessed. The mean follow-up time was 34.7 months (range, 8--47 months). Results: Following limb salvage surgery, no statistical differences were observed in major complications (fracture = 20.0%, control = 12.0%, P = 0.43) or local recurrence complications (fracture = 26.7%, control = 14.0%, P = 0.25). Overall 3-year survival rates of the fracture and control groups (66.7% and 75.3%, respectively) were not statistically different (P = 0.5190). Three-year disease-free survival rates of the fracture and control groups were 53.3% and 66.5%, respectively (P = 0.25). Conclusions: Pathologic fracture was not a prognostic indicator of recurrence or overall survival in localized osteosarcoma patients. Limb salvage can be achieved by and maintaining adequate surgical margins and applying adjuvant chemotherapy.

via World Journal of Surgical Oncology

Role of platelet chemokines, PF-4 and CTAP-III, in cancer biology

With the recent addition of anti-angiogenic agents to cancer treatment, the angiogenesis regulators in platelets are gaining importance. Platelet factor 4 (PF-4/CXCL4) and Connective tissue activating peptide III (CTAP-III) are two platelet-associated chemokines that modulate tumor angiogenesis, inflammation within the tumor microenvironment, and in turn tumor growth. Here, we review the role of PF-4 and CTAP-III in the regulation of tumor angiogenesis; the results of clinical trial using recombinant PF-4 (rPF-4); and the use of PF-4 and CTAP-III as cancer biomarkers.

via Journal of Hematology & Oncology

Sudden hearing loss raises ED alarm

Clinicans should be alert to the development of erectile dysfunction in patients with sudden sensorineural hearing loss, say the authors of a population-based study from Taiwan.

via Med Wire News

Increased invasion and tumorigenicity capacity of CD44+/CD24- breast cancer MCF7 cells in vitro and in nude mice

Background: Identification of cancer stem cells (CSCs) and their behaviors will provide insightful information for the future control of human cancers. This study investigated CD44 and CD24 cell surface markers as breast cancer CSC markers in vitro and in vivo. Methods: Flow cytometry with CD44 and CD24 markers was used to sort breast cancer MCF7 cells for scanning electron microscopy (SEM), tumor cell invasion assay, and nude mouse xenograft assay. Results: Flow cytometry assay using CD44 and CD24 markers sorted MCF7 cells into four subsets, i.e., CD44+/CD24-/low, CD44-/CD24+, CD44+/CD24+, and CD44-/CD24-. The SEM data showed that there were many protrusions on the surface of CD44+/CD24-/low cells. CD44+/CD24-/low cells had many microvilli and pseudopodia. The CD44+/CD24-/low cells had a higher migration and invasion abilities than that of the other three subsets of the cells. The in vivo tumor formation assay revealed that CD44+/CD24- cells had the highest tumorigenic capacity compared to the other three subsets. Conclusion: CD44 and CD24 could be useful markers for identification of breast CSCs because CD44+/CD24-/low cells had unique surface ultrastructures and the highest tumorigenicity and invasive abilities.

via Cancer Cell International

An in-vitro animal experiment on metal implants' thermal effect on radiofrequency ablation

Background: To explore metal implants' thermal effect on radiofrequency ablation (RFA) and ascertain distance-thermal relationship between the metal implants and radiofrequency (RF) electrode. Methods: Metal implants models were established in seven in-vitro porcine livers using silver clips or 125I seeds. RFA were conducted centering the RF electrode axis1 cm away from them, with one side containing a metal implants model the test group and the other side the control group. The thermometric needles were used to measure multi-point temperatures in order to compare the time-distance-temperature difference between the two groups. The gross scopes of the ablation of the two groups were measured and the tissues were analyzed for microscopic histology. Results: At the ablation times of 8, 12,and 15 min, the average multi-point temperatures of the test group and the control group were 48.2+/-18.07[degree sign]C, 51.5+/-19.57[degree sign]C, 54.6+/-19.75[degree sign]C, and 48.6+/-17.69[degree sign]C, 52.2+/-19.73[degree sign]C, 54.9+/-19.24[degree sign]C, respectively, and the differences were not statistically significant (n=126, P>0.05). At the ablation times of 12 and 15 min, the ablation scopes of the test group and the control group were (horizontal/longitudinal diameter) 1.55/3.48 cm, 1.89/3.72 cm, and 1.56/3.48 cm, 1.89/3.72 cm, respectively, and the differences were not statistically significant (n=14, P>0.05). The two groups had the same manifestations in microscopy. Conclusions: Metal implants do not cause significant thermal effect on RFA.

via World Journal of Surgical Oncology

Visceral fat changes after distal gastrectomy according to type of reconstruction procedure for gastric cancer

A case of 'fat-free' pleomorphic lipoma occurring in the upper back and axilla simultaneously

Pleomorphic lipoma is a rare neoplasm that predominantly occurs in the dermis or subcutis of the posterior neck, upper back, and shoulders. Although pleomorphic lipoma is a benign tumor, it may contain atypical cells. As a variant of spindle cell lipoma, pleomorphic lipoma clinically presents as a slow-growing and well-circumscribed subcutaneous mass. Rarely, some patients have multiple lesions. Histologically, pleomorphic lipoma is composed of mature fat, bland spindle-shaped mesenchymal cells, and coarse 'rope-like' collagen bands. In addition, lipoma contains multinucleated floret-like giant cells. Although spindle cell lipoma/pleomorphic lipoma with little fat was seen in the original series described by Enzinger and Harvey, cases with little to no fat remain diagnostically challenging. Herein, we report a case of 'fat-free' pleomorphic lipoma occurring in the upper back and axilla simultaneously. Although the lipoma was typically composed of bland spindle-shaped cells, rope-like collagen, scattered floret-like giant cells, and striking stromal myxoid change in the background, mature fat was absent. Immunohistochemical analyses showed positive staining for CD34, vimentin, and Bcl-2, and negative staining for S100, confirming the diagnosis of pleomorphic lipoma.

via World Journal of Surgical Oncology

Incidence and risk factors for postsurgical gastroparesis syndrome after laparoscopic and open radical gastrectomy

Background: The aim of this study was to investigate the differences and influencing factors for postsurgical gastroparesis syndrome incidence after laparoscopic and open radical gastrectomy. Methods: Clinical data were collected for 563 patients who underwent open radical gastrectomy for gastric cancer and 72 cases receiving laparoscopic radical gastrectomy. We retrospectively analyzed the incidence of postsurgical gastroparesis syndrome, clinical features, course of disease, and risk factors of these two groups. Results: There was no statistical difference for the incident rate of postsurgical gastroparesis syndrome between laparoscopic and open radical gastrectomy (6.9% vs. 3.7%, P > 0.05). Preoperative outflow tract obstruction and Billroth II anastomosis were the two risk factors for postsurgical gastroparesis syndrome in the open radical gastrectomy group and the laparoscopic surgery for gastric cancer group. The same results were obtained from logistic regression statistical analysis. Age greater than 70 years was also one of the risk factors for postsurgical gastroparesis syndrome in the open radical gastrectomy group (P < 0.05). Conclusions: Laparoscopic radical gastrectomy for gastric cancer does not increase the incident rate of postsurgical gastroparesis syndrome.

via World Journal of Surgical Oncology

A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial

Background: There is an unmet need for treatment options in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Lenalidomide plus low-dose dexamethasone is effective and generally well tolerated in Caucasian RRMM patients, but no previous study has evaluated this regimen in Chinese RRMM patients. Methods: MM-021 is a phase 2, multicenter, single-arm open-label registration trial conducted to assess the efficacy, safety, and pharmacokinetics of lenalidomide plus low-dose dexamethasone in Chinese patients with RRMM. Patients with >=1 prior antimyeloma therapy received lenalidomide plus low-dose dexamethasone until disease progression or discontinuation. Follow-up of surviving patients continued for >=1 year after enrollment. The lenalidomide dose was 25 mg/day, and was adjusted according to baseline renal function. Most patients had advanced disease (85.6% had Durie-Salmon stage III) and were heavily pretreated (56.7% had received >=4 prior regimens; 69.5% prior thalidomide and 63.1% prior bortezomib); 5.3% had immunoglobulin D (IgD) disease. Results: The safety population comprised 199 eligible patients. In the efficacy population (n = 187), the disease control rate (at least stable disease) was 94.7%, and the overall response rate (at least partial response) was 47.6%. High response rates were also achieved in patients who had renal impairment and in those with IgD disease. After a median study follow-up of 15.2 months, the median response duration was 8.8 months (range, 0.4--18.8 months) and median progression-free survival was 8.3 months (95% CI 6.5--9.8). The most common grade 3--4 adverse events (AEs) were anemia (26.1%), neutropenia (25.1%), thrombocytopenia (14.6%), pneumonia (13.1%), leukopenia (9.5%), and decreased neutrophil count (8.5%). AEs led to lenalidomide dose reduction and/or interruption in 40.2% of patients, and treatment discontinuation in about 9% of patients. The pharmacokinetic profile of lenalidomide was similar to that reported in Caucasian and Japanese patients. Conclusions: Lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with RRMM, including those with renal impairment and IgD subtype. These findings highlight the clinical potential of this regimen in Chinese RRMM patients who have exhausted current treatment options.Trial registration: China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209 L10808; 209 L10809; 209 L10810; and 209 L10811) and ClinicalTrials.gov identifier: NCT01593410.

via Journal of Hematology & Oncology

Clinicopathological features and CCT2 and PDIA2 expression in gallbladder squamous/adenosquamous carcinoma and gallbladder adenocarcinoma

Background: Gallbladder cancer (GBC) is a relatively uncommon carcinoma among gastrointestinal cancers and usually has a rather poor prognosis. The most common subtype of GBC is adenocarcinoma (AC), which accounts for about 90% of GBC. Squamous carcinoma/adenosquamous carcinoma (SC/ASC) are comparatively rare histopathological subtypes of GBC. The clinicopathological features and biological behaviors of SC/ASC have not been well-characterized. No molecular biomarkers are currently available for predicting the progression, metastasis, and prognosis of the SC/ASC subtype of GBC. Methods: We examined the expression levels of CCT2 and PDIA3 by immunohistochemistry (IHC) staining in human GBC tissue samples collected from 46 patients with SC/ASC and evaluated the clinicopathological significance of both CCT2 and PDIA3 expression in the SC/ASC subtypes of GBC by Kaplan-Meier analysis and multivariate Cox regression analysis. For comparison, we included specimens from 80 AC patients in our study to investigate the specificity of CCT2 and PDIA3 expression in GBC subtypes. Results: We found that the positive expression of CCT2 and PDIA3 was significantly associated with clinicopathological features of both SC/ASC and AC specimens, including high TNM stage and lymph node metastasis. Univariate analysis revealed that the two-year survival rate was significantly lower for patients with positive expression of CCT2 and PDIA3 than for those with negative expression. Multivariate analysis also indicated that the positive expression of CCT2 and PDIA3 was negatively correlated with poor postoperative patient survival and positively correlated with high mortality. Conclusions: Our study suggests that positive expression of CCT2 or PDIA3 is associated with tumor progression and the clinical behavior of gallbladder carcinoma. Therefore, CCT2 and PDIA3 could be potentially important diagnostic and prognostic biomarkers for both SC/ASC and AC subtypes of GBC.

via World Journal of Surgical Oncology

Polyp growth identifies colorectal cancer

Monitoring colorectal polyp growth with computed tomography could help target treatment in patients undergoing routine colorectal cancer surveillance, research suggests.

via Med Wire News

Ovarian granulosa cell tumors: a retrospective study of 27 cases and a review of the literature

Background: Granulosa tumors were described for the first time in 1855 by Rokitansky. These tumors are malignancies with a relatively favorable prognosis. They are characterized by a prolonged natural history and a tendency to late recurrences. The aim of this study is to investigate the epidemiological and pathological characteristics of granulosa cell tumors and to investigate the prognosis factor for recurrences. Methods: The clinical data of patients who were treated in the period from January 2003 to December 2010 at the National Institute of Oncology in Rabat, Morocco for adult granulosa cell tumors of the ovary were investigated retrospectively. Data for age, clinical manifestation, imaging, diagnosis and treatment of the patients were reviewed and analyzed. Post-operative histology was obtained for all patients. Results: Twenty-seven cases were retrieved. The median patient age was 53 years. The most common clinical manifestations at diagnosis were abdominal pain and vaginal bleeding. Mean tumor size was 14 cm.The majority of patients had stage I (63%, n = 17), while (18,5%, n = 5) had stage III, (7.4%, n = 2) had stage IV, and (11%, n = 3) of patients had an unknown stage.In the follow-up period (median = 63.44 months), five (18.51%) patients relapsed. The median time to relapse was 41.8 months, (range: 18 to 62 months). Conclusions: Granulosa cell tumor of the ovary is an uncommon neoplasm. The adult form progresses slowly and often is diagnosed in an early stage of disease. Surgery is indicated. A prolonged post-therapeutic follow-up is necessary because of the risk of recurrences, late and exceptional for the adult form.

via World Journal of Surgical Oncology

Overexpression of HSPA2 is correlated with poor prognosis in esophageal squamous cell carcinoma

Background: Heat shock-related 70 kDa protein 2 (HSPA2) has been identified as a potential cancer-promoting protein expressed at abnormal levels in a subset of cancers. However, its important role in esophageal squamous cell carcinoma (ESCC) is hardly known by people. The purpose of this study is to assess HSPA2 expression and to explore its role in ESCC. Methods: Thirty ESCC samples, paired adjacent non-cancerous tissues and normal esophageal tissues, were collected for HSPA2 detection by quantitative RT-PCR (qRT-PCR) and western blotting. Additionally, the expression of HSPA2 in ESCC and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry, and correlated with clinicopathological parameters and patients' outcome. Results: HSPA2 mRNA and protein were overexpressed in ESCC tissues. Overexpression of HSPA2 was significantly associated with primary tumor, TNM stage, lymph node metastases and recurrence, respectively (all, P <0.05). Kaplan-Meier curves showed that elevated HSPA2 expression was associated with shorter disease-free survival and overall survival in ESCC patients. Cox multivariate regression analysis revealed that overexpression of HSPA2 was an independent prognostic factor in disease-free survival and overall survival for ESCC patients (hazard ratio was 2.115 and 2.210, respectively, P <0.05). Conclusions: Our findings demonstrate that overexpression of HSPA2 may contribute to the malignant progression of ESCC and present a novel prognostic indicator for ESCC patients.

via World Journal of Surgical Oncology

Novel agents and biomarkers for acute lymphoid leukemia

New genetic markers for adult acute lymphoblastic leukemia (ALL) have been found to have prognostic impact, such as the lymphoid transcription factor gene IKZF1 alterations, which are associated with a high rate of leukemic relapse in B-ALL. Although complete remission rates by induction chemotherapy in ALL are now high, the long-term survival is still disappointing. Improvements in the survival outcome of ALL have been observed in young adults as a result of the use of pediatric inspired regimens and the broadening of the number of patients who are eligible for allogeneic SCT. Development of new and less toxic agents also provide promise to improve the outcome in adult ALL, such as tyrosine kinase inhibitors in Ph-positive ALL, rituximab in CD20-positive disease, blinatumomab in precursor B-ALL and nelarabine in T-lineage ALL. Challenges for the future are to implement genomic profiling into the clinical setting to guide risk stratification and providing novel targets for tailored therapies.

via Journal of Hematology & Oncology

Nip the HPV encoded Evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes

HPV encoded proteins can elicit ectopic protein--protein interactions that re-wire signaling pathways, in a mode that promotes malignancy. Moreover, accumulating data related to HPV is now providing compelling substantiation of a central role played by HPV in escaping immunosurveillance and impairment of apoptotic response. What emerges is an intricate network of Wnt, TGF, Notch signaling cascades that forms higher-order ligand--receptor complexes routing downstream signaling in HPV infected cells. These HPV infected cells are regulated both extracellularly by ligand receptor axis and intracellularly by HPV encoded proteins and impair TRAIL mediated apoptosis. We divide this review into different sections addressing how linear signaling pathways integrate to facilitate carcinogenesis and compounds that directly or indirectly reverse these aberrant interactions offer new possibilities for therapy in cancer. Although HPV encoded proteins mediated misrepresentation of pathways is difficult to target, improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can target dysregulated pathways in HPV infected cervical cancer cells, thus setting the stage for preclinical models and clinical trials.

via Cancer Cell International

Does geography influence the treatment and outcomes of colorectal cancer? A population-based analysis

Background: The Canadian province of Manitoba covers a large geographical area but only has one major urban center, Winnipeg. We sought to determine if regional differences existed in the quality of colorectal cancer care in a publicly funded health care system. Methods: This was a population-based historical cohort analysis of the treatment and outcomes of Manitobans diagnosed with colorectal cancer between 2004 and 2006. Administrative databases were utilized to assess quality of care using published quality indicators. Results: A total of 2,086 patients were diagnosed with stage I to IV colorectal cancer and 42.2% lived outside of Winnipeg. Patients from North Manitoba had a lower odds of undergoing major surgery after controlling for other confounders (odds ratio (OR): 0.48, 95% confidence interval (CI): 0.26 to 0.90). No geographic differences existed in the quality measures of 30-day operative mortality, consultations with oncologists, surveillance colonoscopy, and 5-year survival. However, there was a trend towards lower survival in North Manitoba. Conclusion: We found minimal differences by geography. However, overall compliance with quality measures is low and there are concerning trends in North Manitoba. This study is one of the few to evaluate population-based benchmarks for colorectal cancer therapy in Canada.

via World Journal of Surgical Oncology

Early motherhood reduces kidney cancer risk

Data from Taiwan suggest that a younger age at first birth may be protective against kidney cancer in women.

via Med Wire News

Expression of ALDH1 in breast invasive ductal carcinoma: an independent predictor of early tumor relapse

Background: The specific mechanism underlying the contribution of the Aldehyde dehydrogenase 1 (ALDH1) phenotype to metastatic behavior and early tumor relapse in breast cancer is currently unclear. Methods: 147 randomly selected invasive ductal carcinoma samples were assayed for expression of ALDH1A1, NOTCH1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), and association of the ALDH1A1 phenotype with clinic pathological features was further evaluated. Results: ALDH1A1-positive cells were detected in 63.3% (93 of 147) of tumors. 80.0% (32 of 40) of tumors with strong ALDH1A1 staining displayed early recurrence, compared with 20.0% (8 of 40) of tumors negative for ALDH1A1 expression (P = 0.027). ALDH1A1 status was significantly correlated with strong malignant proliferative marker Ki67 staining (P = 0.001), and no significantly different expression of ALDH1A1 across the subtypes of ER, PR, and HER2 expression and triple negative features of tumor tissue. Multivariate regression analysis demonstrated that elevated ALDH1A1 expression is an independent predictor of recurrence-free survival and distant metastasis-free survival. Notably, breast cancer tissue strong for ALDH1A1 expression displayed weak NOTCH1 staining compared to ALDH1A1 weak tumor tissue (P = 0.002), and the relationship between ALDH1A1 and NOTCH1 mRNA positivity was significant (Pearson correlation - 0.337, P = 0.014; Spearman's rho - 0.376, P = 0.006). Elevated NOTCH1 mRNA level (using a cut-off value based on the median ALDH1A1 2-[white up-pointing triangle][white up-pointing triangle]CT value) was associated with reduction of ALDH1A1 mRNA level (P = 0.001). Conclusions: The ALDH1A1 phenotype is an independent predictor of early tumor relapse characteristic (specifically, incidence of early local recurrence and distant metastasis) of invasive ductal carcinoma. The NOTCH1 signaling pathway is possibly involved in the negative association of the ALDH1A1 phenotype with early malignant relapse in invasive ductal carcinoma.

via Cancer Cell International

Pure mucinous carcinoma of the breast: clinicopathologic characteristics and long-term outcome among Taiwanese women

Background: Pure mucinous carcinoma (MC) is found in about 3.5% of all newly diagnosed breast cancer patients in Taiwan. MC is a relatively rare malignancy of breast cancer, and its nature, behaviors, treatment pattern and long-term follow-up are not well understood. The study aimed to investigate the incidence rate, treatment patterns, and prognostic factors of MC of the breast and the clinical long-term outcomes compared with infiltrating ductal carcinoma not otherwise specified (IDC) in the middle and south Taiwanese women. Methods: Data from 93 patients with breast MC were retrospectively reviewed and the clinicopathologic characteristics and survival status were compared with those of 2,674 patients with IDC. Results: The expression of hormonal receptor was higher in MC than those in IDC (P <0.001). MC also demonstrated lower Her2/neu gene over-expression (P = 0.023), less axillary lymph node involvement (P <0.0001), lymphovascular invasion (P <0.0001) and higher 10-year overall survival rate (P = 0.042), when compared with those of IDC. Conclusion: Our data confirm the less aggressive behavior of MC compared to IDC. MC showed favorable clinicopathologic characteristics in tumor grade, hormone receptor status and lymph node involvement in the middle and south Taiwanese women.

via World Journal of Surgical Oncology

Focused abdominal ultrasound in preoperative liver surgery staging: a prospective study

Background: Because of its safety, relative low cost and widespread availability, conventional ultrasound (US) is the modality of choice for initial evaluation of the liver. Following US, in patients eligible for surgery, further computed tomography and/or magnetic resonance imaging is usually recommended for surgical planning. There are no recent published series focusing on conventional abdominal US exclusively employed for the evaluation of liver nodules before surgery. The objective of this study is to evaluate the efficacy of focused conventional preoperative US in detecting liver lesions, and the impact of US findings on surgical management. Methods: Sixty-seven noncirrhotic patients underwent surgical resection, after being previously submitted to focused liver US evaluation. US results were compared with intraoperative US (IOUS) and histology (gold standard). The IOUS was performed by the same radiologist who performed the preoperative US. Patient-by-patient and lesion-by-lesion analyses were performed. Results: A total of 241 lesions were depicted in 67 patients. The mean number of lesions detected per patient by US and IOUS was 2.37 and 3.37, respectively (P = 0.001). In 52.2% of patients, US and IOUS depicted the same number of liver lesions. Surgery with curative intent was conducted in 61 (91.0%) patients. Histological evaluation was obtained in 196 lesions; 155 were considered malignant. The overall lesions detection rate by US was 65.6%. For lesions <15 mm and lesions >=15 mm, US showed a sensitivity rate of 55.3% and 75.5%, respectively. Conclusions: The relatively high sensitivity rates achieved by US focused on liver evaluation, with the aim of lowering costs but not efficiency, places the method in focus again for use in the routine preoperative staging of candidates for liver resection. We suggest for preoperative evaluation that US could be associated with one section imaging method (computed tomography or magnetic resonance imaging) as routine.

via World Journal of Surgical Oncology

The estimation of metaloproteinases and their inhibitors blood levels in patients with pancreatic tumors

Background: The aim of the study was to evaluate the concentration of proteolytic enzymes, MMP-2 and MMP-9, and their tissue inhibitors, TIMP-1 and TIMP-2, in the blood of patients with benign and malignant pancreatic tumors. Methods: MMP-2, MMP-9, TIMP-1, and TIMP-2 were evaluated in the patients with benign and malignant pancreatic tumors before surgery and in the 30-day follow-up. The study covered 134 patients aged 54 to 76 years, who were divided into groups by TNM staging. Results: Before the operation, the highest mean concentration of MMP-2 was found in patients with unresectable cancer, whereas the highest level of MMP-9 was in patients with resectable cancer. The highest level of TIMP-1 was noted in patients with inflammatory tumors. In 1 month following the operation, the highest level of MMP-2 was also in patients with unresectable cancer and the highest level of TIMP-2 in patients with inflammatory tumors. Conclusions: The evaluation of the level of the studied cytokines in the pancreatic tumor patients can be diagnostically significant in the differentiation of benign and malignant changes. The changes in the levels of the studied enzymes and their inhibitors can have a prognostic value in the clinical severity of pancreatic cancer.

via World Journal of Surgical Oncology

The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection

Background: The expression of CK19 in primary hepatocellular carcinoma (HCC) is associated with a poor outcome. However, few studies have investigated the expression profile of CK19 in regional lymph nodes (LNs) of HCC after hepatic resection. The purpose of this study was to evaluate the expression of CK19 in primary liver tumor and regional LNs of HCC with and without lymph node metastasis (LNM). Methods: The expression of CK19 in patients with (n = 16) and without LNM (n = 26) was examined using immunohistochemical staining. Both the primary tumor and LN specimen were studied for their CK19 expression. Clinico-pathological variables and prognostic significance were analyzed. Results: Immunopositivity of CK19 in primary liver tumor was significantly correlated with LNM (P = 0.005) and tumor non-encapsulation (P <0.005). Univariate analysis showed that CK19 expression in primary liver tumor, CK19 expression in regional LN, vascular invasion, daughter nodules, positive resection margin and American Joint Committee on Cancer (AJCC) tumor stage significantly decreased overall survival. Multivariate analysis demonstrated that daughter nodules (P = 0.001) and CK19 expression in regional LN (P = 0.002) were independent prognostic factors for overall survival. Conclusions: This study showed that CK19 expression in regional LN of HCC was associated with LNM and an extremely poor outcome after operation. It is of clinical significance to identify these patients at risk for more aggressive HCC, and multi-modality treatment could be helpful to improve their dismal outcome.

via World Journal of Surgical Oncology

Bronchioloalveolar carcinoma as a second malignancy in a pediatric osteosarcoma survivor: case report

Background: Primary lung cancer is extremely rare in children, while secondary malignancies reportedly develop in 2% to 3% of pediatric osteosarcoma survivors.Case presentationA 14-year-old girl was found to have two pulmonary lesions on computed tomography. These tumors had developed 1 year after osteosarcoma surgery. Segmentectomy of right segment 1 and wedge resection of right segment 9 were performed. Both lesions were completely resected and postoperative histopathological examination revealed metastasis of osteosarcoma and bronchioloalveolar carcinoma, respectively. Conclusion: Bronchioloalveolar carcinoma may present as a solitary pulmonary lesion indistinguishable from a metastatic lesion and should be included in the differential diagnosis of pulmonary lesions in survivors of pediatric cancer. Thus, pulmonary lesions identified in these patients should be biopsied or resected to establish a histological diagnosis.

via World Journal of Surgical Oncology

Sequential preoperative hepatic vein embolization after portal vein embolization for extended left hepatectomy in colorectal liver metastases

Background: The role of portal vein embolization to increase future liver remnant (FLR) is well-established in the treatment of colorectal liver metastases. However, the role of hepatic vein embolization is unclear.Case report: A patient with colorectal liver metastases received neoadjuvant chemotherapy prior to attempted resection. At the time of resection his tumor appeared to invade the left and middle hepatic vein, requiring an extended left hepatectomy including segments five and eight. Post-operatively, he underwent sequential left portal vein embolization followed by left hepatic vein embolization and finally, middle hepatic vein embolization. Hepatic vein embolization was performed to increase the FLR as well as to allow collateral drainage of the FLR to develop. A left trisectionectomy was then performed and no evidence of postoperative liver congestion or morbidity was found. Conclusion: Sequential portal vein embolization and hepatic vein embolization for extended left hepatectomy may be considered to increase FLR and may prevent right hepatic congestion after sacrificing the middle vein.

via World Journal of Surgical Oncology

Clinicopathological analysis of colorectal cancer: a comparison between emergency and elective surgical cases

Background: Approximately 15 to 30% of colorectal cancers present as an emergency, most often as obstruction or perforation. Studies report poorer outcome for patients who undergo emergency compared with elective surgery, both for their initial hospital stay and their long-term survival. Advanced tumor pathology and tumors with unfavorable histologic features may provide the basis for the difference in outcome. The aim of this study was to compare the clinical and pathologic profiles of emergency and elective surgical cases for colorectal cancer, and relate these to gender, age group, tumor location, and family history of the disease. The main outcome measure was the difference in morphology between elective and emergency surgical cases. Methods: In total, 976 tumors from patients treated surgically for colorectal cancer between 2004 and 2006 in Stockholm County, Sweden (8 hospitals) were analyzed in the study. Seventeen morphological features were examined and compared with type of operation (elective or emergency), gender, age, tumor location, and family history of colorectal cancer by re-evaluating the histopathologic features of the tumors. Results: In a univariate analysis, the following characteristics were found more frequently in emergency compared with elective cases: multiple tumors, higher American Joint Committee on Cancer (AJCC), tumor (T) and node (N) stage, peri-tumor lymphocytic reaction, high number of tumor-infiltrating lymphocytes, signet-ring cell mucinous carcinoma, desmoplastic stromal reaction, vascular and perineural invasion, and infiltrative tumor margin (P<0.0001 for AJCC stage III to IV, N stage 1 to 2/3, and vascular invasion). In a multivariate analysis, all these differences, with the exception of peri-tumor lymphocytic reaction, remained significant (P<0.0001 for multiple tumors, perineural invasion, infiltrative tumor margin, AJCC stage III, and N stage 1 to 2/3). Conclusions: Colorectal cancers that need surgery as an emergency case generally show a more aggressive histopathologic profile and a more advanced stage than do elective cases. Essentially, no difference was seen in location, and therefore it is likely there would be no differences in macro-environment either. Our results could indicate that colorectal cancers needing emergency surgery belong to an inherently specific group with a different etiologic or genetic background.

via World Journal of Surgical Oncology

Rapid induction of complete molecular remission by sequential therapy with LDAC and sorafenib in FLT3-ITD-positive patients unfit for intensive treatment: two cases and review of the literature

Treatment of acute myeloid leukemia remains a therapeutic challenge. Even in younger patients with a low rate of co-morbidities less than 50% of patients can be cured. For older patients or patients with significant co-morbidities, the situation appears even worse. In patients not eligible for intensive treatment approaches - e.g. due to underlying medical conditions - therapeutic approaches remain almost exclusively palliative. However, even with less intense treatment approaches, temporary remission can be achieved and this contributes to prolonged survival and improved quality of life of the respective patient. Targeted therapies have been widely used as palliative treatment in- and outside clinical trials as single agents. Combination with low-dose cytarabine (LDAC) potentially improves remission rates and can be safely administered in an outpatient setting.Previous studies showed that additive hematologic toxicity of combinatory therapeutic approaches may arise from simultaneous treatment (e.g. chemotherapy plus targeted therapies). However, sequential therapies have already proven their feasibility in clinical trials. Here, we report two cases of rapid induction of complete molecular remission by sequential therapy with LDAC and sorafenib in patients unfit for intensive chemotherapy without significant long-term toxicity.

via Journal of Hematology & Oncology

Role of relaxin-2 in human primary osteosarcoma

Background: The aim of this study was to clarify the clinicopathological outcome of serum relaxin-2 and tissues relaxin-2 expression levels in human primary osteosarcoma (OS), and to explore the roles of relaxin-2 inhibition and determine its possibility as a therapeutic target in human osteosarcoma. Methods: Real-time quantitative RT-PCR assay was performed to detect the expression of relaxin-2 mRNA in 36 cases of human osteosarcoma tissue samples. Serum relaxin-2 levels was measured in ELISA-based method in the 36 cases of osteosarcoma and 50 cases of controls. MTT and TUNEL assay was used to detect cell proliferation and apoptosis after relaxin-2 knockdown with siRNA transfection for 48 hs in vitro. Matrigel invasion and angiogenesis formation assay was used to detect cell metastasis and angiogenesis with HMEC-1 endothelial cells after relaxin-2 knockdown with siRNA transfection for 48 hs in vitro.The effects of relaxin-2 knockdown with anti- relaxin-2 mAb treatment on growth, apoptosis angiogenesis formation and lung metastasis in vivo was analyzed. Results: The results showed the levels of relaxin-2 mRNA expression in osteosarcoma tissue samples were significantly higher than those in the corresponding non-tumor tissue samples (P < 0.01), and the serum relaxin-2 levels were significantly higher in OS patients than in healthy controls (P < 0.01). The incidence of advanced stage cancer and hematogenous metastasis cancer in the high relaxin-2 mRNA expression group and high serum relaxin-2 levels groups was significantly higher than that in the low relaxin-2 expression group and low serum relaxin-2 levels groups ,respectively. Knockdown of relaxin-2 by siRNA transfection in vitro inhibited proliferation, invasion and angiogenesis in vitro in MG-63 OS cells. In vivo, knockdown of relaxin-2 with anti- relaxin-2 mAb treatment inhibited tumor growth by 62% (P < 0.01) and the formation of lung metastases was inhibited by 72.4% (P < 0.01). Microvascular density was reduced more than 60% due to anti- relaxin-2 mAb treatment (P < 0.01). Conclusions: Our study suggests that overexpression of relaxin-2 is critical for the metastasis of human osteosarcoma. Detection of relaxin-2 mRNA expression or serum relaxin-2 levels may provide the first biological prognostic marker for OS. Furthermore, relaxin-2 is the potential molecular target for osteosarcoma therapy.

via Cancer Cell International

Single nucleotide polymorphisms of CD20 gene and their relationship with clinical efficacy of R-CHOP in patients with diffuse large B cell lymphoma

Background: R-CHOP has significantly improved survival rates of patients with diffuse large B cell lymphoma (DLBCL) by ~20% as compared to CHOP. CD20 antigen, highly expressed on more than 80% of B-cell lymphomas, is the target for rituximab. The goal of our study was to examine polymorphism in the CD20 gene in Chinese DLBCL population and whether CD20 gene polymorphism is associated with clinical response to R-CHOP.MethodCD20 gene polymorphism was detected in the entire coding regions (CDS) including 6 exons by polymerase chain reaction (PCR)-sequencing assay in 164 patients with DLBCL. Among them, 129 patients treated with R-CHOP as frontline therapy (R >= 4 cycles) were assessable for the efficacy. Results: Polymorphisms at three single nucleotides (SNP) were identified in the entire coding regions of the CD20 gene in the 164 patients. One of them, CD20 Exon2 [216] was found to be highly correlated with response to R-CHOP. Patients with homozygous C genotype showed a trend toward higher overall response rate than others with CT plus TT genotype (90.6% vs. 79.5%; P =0.166). A trend toward higher complete remission (CR) rate was observed in patients with homozygous C genotype (67.4%) compared with CT plus TT genotype (47.1%) (P = 0.091). Conclusion: These results suggest that there are 3 SNPs in CDS of the CD20 gene in Chinese DLBCL population. The CC genotype at Exon2 [216] appears to be associated with favourable response to R-CHOP.

via Cancer Cell International

Transperineal prostate biopsy shows core–complication connection

Research shows that clinical complications after transperineal prostate biopsy are common, but rarely result in hospital admission.

via Med Wire News

The effects of a histone deacetylase inhibitor on biological behavior of diffuse large B-cell lymphoma cell lines and insights into the underlying mechanisms

Background: Epigenetic control using histone deacetylase (HDAC) inhibitors is a promising therapy for lymphomas. Insights into the anti-proliferative effects of HDAC inhibitors on diffuse large B-cell lymphoma (DLBCL) and further understanding of the underlying mechanisms, which remain unclear to date, are of great importance. Methods: Three DLBCL cell lines (DoHH2, LY1 and LY8) were used to define the potential epigenetic targets for Trichostatin A (TSA)-mediated anti-proliferative effects via CCK-8 assay. Cell cycle distribution and apoptosis were detected by flow cytometry. We further investigated the underlying molecular mechanisms by examining expression levels of relevant proteins using western blot analysis. Results: TSA treatment inhibited the growth of all three DLBCL cell lines and enhanced cell cycle arrest and apoptosis. Molecular analysis revealed upregulated acetylation of histone H3, alpha-tubulin and p53, and dephosphorylation of pAkt with altered expression of its main downstream effectors (p21, p27, cyclin D1 and Bcl-2). HDAC profiling revealed that all three cell lines had varying HDAC1--6 expression levels, with the highest expression of all six isoforms, in DoHH2 cells, which displayed the highest sensitivity to TSA. Conclusion: Our results demonstrated that the HDAC inhibitor TSA inhibited DLBCL cell growth, and that cell lines with higher expression of HDACs tended to be more sensitive to TSA. Our data also suggested that inhibition of pAkt and activation of p53 pathway are the main molecular events involved in inhibitory effects of TSA.

via Cancer Cell International

GP73 is down-regulated in gastric cancer and associated with tumor differentiation

Background: Golgi protein 73 (GP73) is a type II Golgi transmembrane protein. It is over-expressed in several cancers, including hepatocellular carcinomas, bile duct carcinomas, lung cancer and prostate cancer. However, there are few reports of GP73 in gastric cancer. This study is aimed at investigating the expression of GP73 and its relationship with clinical pathological characters in gastric cancer. Methods: GP73 mRNA level was determined by quantitative real-time RT-PCR in 41 pairs of matched gastric tumorous tissues and adjacent non-tumorous mucosal tissues. Western blotting was also performed to detect the GP73 protein level. GP73 protein expression was analyzed by immunohistochemistry in 52 clinically characterized gastric cancer patients and 10 non-tumorous gastric mucosal tissue controls. Results: The mRNA and protein level of GP73 were significantly down-regulated in gastric tumorous tissues compared with the non-tumorous mucosal tissues. In non-tumorous mucosa, strong diffuse cytoplasmic staining can be seen in cells located at the surface of the glandular and foveolar compartment; while in tumorous tissues, the staining was much weaker or even absent, and mainly in a semi-granular dot-like staining pattern. The expression level of GP73 protein was associated with patients' gender and tumor differentiation. Conclusions: GP73 was normally expressed in non-tumorous gastric mucosa and down-regulated in gastric cancer. Its expression in gastric cancer was correlated with tumor differentiation.

via World Journal of Surgical Oncology

Age, node status predict lung cancer surgery survival

Age and node status are the strongest prognostic factors for patients considering T4 lung cancer resection, results from the Japanese Lung Cancer Registry show.

via Med Wire News

Silenced miR points to poor SCLC prognosis

Chinese scientists have identified a molecular marker that significantly predicts the survival of patients with small-cell lung cancer.

via Med Wire News

Postoperative outcomes following pancreaticoduodenectomy: how should age affect clinical practice?

Background: Pancreaticoduodenectomy is an increasingly common procedure performed for both benign and malignant disease. There are conflicting data regarding the safety of pancreatic resection in older patients. Potentially modifiable perioperative risk factors to improve outcomes in older patients have yet to be determined. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database for 2008 to 2009 was used for this retrospective analysis. Patients undergoing pancreaticoduodenectomy were identified and divided into those above and below the age of 65. Preoperative risk factors and postoperative morbidity and mortality were evaluated. Results: Among 2,045 patients included in this analysis, 994 patients were >65 years (48.6%) while 1,051 were (less than or equal to) 65 years (51.4%). Thirty-day mortality was higher in the older age group compared to the younger age group 3.6% vs. 1.9% respectively, P = 0.017, odds ratio 1.94. Older patients had a higher incidence of unplanned intubation, ventilator support >48 h and septic shock compared with younger patients. On multivariate logistic regression, after adjusting for other 30-day postoperative occurrences (significant at the P <0.1 level) only septic shock was independently associated with a higher odds of mortality, unplanned intubation, and ventilator support >48 h in older patients compared with younger patients. Conclusions: This report from a population-based database is the first to highlight postoperative sepsis as an independent risk factor for mortality and morbidity in older patients undergoing pancreatic resection. Careful perioperative management addressing this issue is essential for patients over the age of 65.

via World Journal of Surgical Oncology

The value of chest CT for prediction of breast tumor size: comparison with pathology measurement

Background: Little information is available on the use of chest computed tomography (CT) to predict breast tumor size in breast cancer, despite the fact that chest CT examinations are being increasingly used. The purpose of this study was to evaluate the value of chest CT for predicting breast tumor size using pathology measurements as reference standards. Methods: Tumor sizes (defined as greatest diameter) were retrospectively measured on the preoperative chest CT images of 285 patients with surgically proven unifocal, invasive breast carcinoma. Greatest tumor diameters as determined by chest CT and pathologic examinations were compared by linear regression and Spearman's rho correlation analysis. Concordance between CT and pathology results was defined as a diameter difference of <5 mm. Subgroup analyses were also performed with respect to tumor size (<20 mm or >=20 mm) and histological subtype (invasive ductal carcinoma(IDC) or non-IDC). Results: CT and pathology measured diameters were found to be linearly related (size at pathology = 1.086 x CT determined tumor size - 1.141; Spearman's rho correlation coefficient = 0.84, P<0.001). Most tumors (n = 228, 80.0%) were concordant by chest CT and pathology, but 36 tumors (12.7%) were underestimated by CT (average underestimation,11 mm; range, 6--36 mm) and 21 tumors (7.4%) were overestimated (average overestimation by CT,10 mm; range, 6--19 mm). The concordance rate between the two sets of measurements was greater for tumor of <20 mm and for IDC (P<0.001 and P = 0.011, respectively). Conclusions: Tumor size by chest CT is well correlated with pathology determined tumor size in breast cancer patients, and the diameters of the majority of tumors by chest CT and pathology differed by <5 mm. In addition, the concordance rate was higher for breast tumors of <20 mm and for tumors of the IDC histologic subtype.

via World Journal of Surgical Oncology

Unique clinicopathological features of metaplastic breast carcinoma compared with invasive ductal carcinoma and poor prognostic indicators

Background: Metaplastic breast carcinoma is a rare aggressive malignant neoplasm. The purposes of this study are to review the pathologic features and clinical outcomes of metaplastic breast carcinoma compared to invasive ductal carcinoma and to evaluate the prognosis of metaplastic breast carcinoma. Methods: The cases of 55 patients with metaplastic breast carcinomapresenting between 1991 and 2006 were analyzed and compared to the cases of 767 age-matched patients with invasive ductal carcinoma from the same time period. Results: The group of patients with metaplastic breast carcinoma presented with a larger tumor size, lower lymph node involvement, higher percentage of triple-negative (estrogen receptor-, progesterone receptor- and human epidermal growth factor receptor-2-negative) cases, and Ki-67 over-expression compared with the group of patients with invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Patients in the metaplastic breast carcinoma group tended to have more local (often chest wall) recurrences (P =0.038) and distant (often lung) metastases (P =0.001) than those in the invasive ductal carcinomas group. The prognosis of metaplastic breast carcinoma was poorer than that of invasive ductal carcinoma and triple-negative invasive ductal carcinomas; the 5-year overall survival rate was 54.5% in metaplastic breast carcinoma versus 85.1% in invasive ductal carcinoma, and 73.3% in triple-negative invasive ductal carcinomas (P <0.001). The 5-year disease-free survival rate was 45.5% in metaplastic breast carcinoma versus 71.2% in invasive ductal carcinoma, and 60.3% in triple-negative invasive ductal carcinomas (P <0.001). Multivariate analysis revealed tumor size larger than 5.0 cm, lymph node involvement and Ki-67>=14% were significantly related to 5-year overall survival (P = 0.010; P = 0.010; P = 0.035) and 5-year disease-free survival (P = 0.020; P = 0.018; P = 0.049). Conclusions: Metaplastic breast carcinoma shows a poorer prognosis than both invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Tumor size larger than 5.0 cm, lymph node involvement and Ki-67 >=14% indicate a poor prognosis in patients with metaplastic breast carcinoma.

via World Journal of Surgical Oncology

Locally-advanced primary neuroendocrine carcinoma of the breast: case report and review of the literature

Background: Primary neuroendocrine carcinoma of the breast is a heterogeneous group of rare tumors with positive immunoreactivity to neuroendocrine markers in at least 50% of cells. Diagnosis also requires that other primary sites be ruled out and that the same tumor show histological evidence of a breast in situ component. Primary neuroendocrine carcinoma of the breast rarely presents as locally advanced disease and less frequently with such widespread metastatic disease as described herein. The review accompanying this case report is the first to provide an overview of all the cases of primary neuroendocrine carcinoma of the breast published in the literature and encompasses detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, classification, surgical and adjuvant treatment, as well as prognosis. We also provide recommendations for common clinical and histologic pitfalls associated with this tumor.Case presentationWe describe a case of a 51-year-old Hispanic woman initially diagnosed with locally-advanced invasive ductal carcinoma that did not respond to neodjuvant treatment. After undergoing modified radical mastectomy the final surgical pathology showed evidence of alveolar-type primary neuroendocrine carcinoma of the breast. The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatinum. Thirteen months after surgery the patient is alive, but developed pulmonary, bone, and hepatic metastasis. Conclusion: The breast in situ component of primary neuroendocrine carcinoma of the breast may prevail on a core biopsy samples increasing the probability of underdiagnosing this tumor preoperatively. Being aware of the existence of this disease allows for timely diagnosis and management. Optimal treatment requires simultaneous consideration of both the neuroendocrine and breast in situ tumor features.

via World Journal of Surgical Oncology

Determination of the apoptotic index in osteosarcoma tissue and its relationship with patients prognosis

Background: Nowadays it remains a controversial issue whether a correlation exists between the apoptosis rate of tumor tissue and the prognosis of the patients. We aimed to explore the prognostic significance of apoptosis index of human osteosarcoma tissue. Methods: The technique of terminal DNA breakpoints in situ 3 - hydroxy end labeling (TUNEL) was used to detect and analysis apoptosis index in 56 osteosarcoma specimens. The relationships between apoptosis index of tumor tissue and long term survival of patients as well as pathologic classification, tumor clinical stages, tumor size and level of serum alkaline phosphatase were analyzed. Results: Our studies showed the cases with high apoptosis index had significantly longer survival time. Apoptosis index in osteosarcoma tissue was correlated with tumor size and level of serum alkaline phosphatase but not with pathologic classifications and clinical stages of tumor. Conclusion: Our results demonstrated that apoptosis index of osteosarcoma tissue combined with serum alkaline phosphatase could used as valid indicators to predicate the malignant level and prognosis of osteosarcoma cases, which would contribute to enhance efficacy of clinical treatments for osteosarcoma.

via Cancer Cell International

Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report

Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease.

via World Journal of Surgical Oncology

HER2 screening recommended for lung adenocarcinoma patients

Researchers highlight the importance of testing for HER2 mutations in patients with non-small-cell lung cancer, adding to evidence that supports the use of HER2-targeted drugs in this population.

via Med Wire News

Targeted therapy for HER2 positive breast cancer

IntroductionBreast cancer is the second most common cause of death for women behind lung cancer and the most common cause of cancer deaths for women aged 45--55 years old [1]. Although there continue to be enormously large numbers of disease incidence, deaths have been declining due to the disease with two hallmark time frames. The first occurred during the mid to late 1980's when hormonal therapy was introduced as a treatment for ER/PR positive breast cancer. The second occurred in the late 1990's when trastuzumab was introduced in treating HER2 positive breast cancer. These remarkable accomplishments in developing novel targeted therapies for breast cancer, along with a better understanding of the disease biology have improved disease outcome over the past 20 years.This article reviews the data presented at 2012 American Society of Clinical Oncology and 2012 San Antonio Breast Cancer Symposium regarding progress made in the field of HER2 positive breast cancer and examines the future of HER2 targeted therapy.

via Journal of Hematology & Oncology

Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties

For their various bioactivities, biomaterials derived from marine algae are important ingredients in many products, such as cosmetics and drugs for treating cancer and other diseases. This mini-review comprehensively compares the bioactivities and biological functions of biomaterials from red, green, brown, and blue-green algae. The anti-oxidative effects and bioactivities of several different crude extracts of algae have been evaluated both in vitro and in vivo. Natural products derived from marine algae protect cells by modulating the effects of oxidative stress. Because oxidative stress plays important roles in inflammatory reactions and in carcinogenesis, marine algal natural products have potential for use in anti-cancer and anti-inflammatory drugs.

via Cancer Cell International

Laparoscopic upper vaginectomy for post-hysterectomy high risk vaginal intraepithelial neoplasia and superficially invasive vaginal carcinoma

Background: The aim of this study is to describe the feasibility and efficacy of the laparoscopic upper vaginectomy (LUV) in vaginal intraepithelial neoplasia(VAIN) and superficially invasive vaginal carcinoma. Methods: We studied patients with vaginal intraepithelial neoplasia (VAIN) 2, VAIN 3, and superficially invasive vaginal carcinoma after hysterectomy who have been under laparoscopic upper vaginectomy between March 2010 and March 2012. Results: Four patients underwent LUV after hysterectomy for high risk VAIN and early vaginal cancer. The mean age was 50.8 (range 40--56) years; the mean operation time was 162.5 (range 145--205) minutes; and the mean estimated blood loss was 55 (range 20--100) ml. All the patients restituted bladder function after the removal of the foley catheter. Mean hospital stay was 2 days. Two patients had postoperative complications. One patient with warfarin administration had vaginal stump bleeding and another developed vesico-vaginal fistula. Three of the patients had no residual lesion, but 1 patient had VAIN 1 in the resection margin. Colposcopy was followed on all patients and cytology proved no recurrence. Conclusions: LUV after hysterectomy is a feasible procedure and attentively applicable to high risk VAIN or superficially invasive vaginal carcinoma.

via World Journal of Surgical Oncology

Primary NSCLC shares mutations with metastases

Scientists have found a high level of concordance in the genetic mutations of pairs of primary non-small-cell lung cancer and metachronous or synchronous metastases.

via Med Wire News

KRAS mutation fails to predict NSCLC chemotherapy success

Research casts doubt on the ability of the KRAS mutation to aid the selection of patients with non-small-cell lung cancer to receive adjuvant chemotherapy.

via Med Wire News

Pyuria predicts poor outcome in NMIBC

Japanese research shows that pyuria at diagnosis is independently associated with disease recurrence and progression in patients with non-muscle-invasive bladder cancer.

via Med Wire News

Primary care physicians boost prostate cancer BMD monitoring

A US study has found that rates of bone mineral density testing in men with prostate cancer receiving androgen deprivation therapy are highest among those whose primary care physician is involved in their care.

via Med Wire News

Apigenin promotes apoptosis, inhibits invasion and induces cell cycle arrest of T24 human bladder cancer cells

Background: Apigenin (4',5,7-trihydroxyflavone) was recently shown effective in inhibiting several cancers. The aim of this study was to investigate the effect and mechanism of apigenin in the human bladder cancer cell line T24 for the first time. Methods: T24 cells were treated with varying concentrations and time of apigenin. Cell viability was evaluated by MTT assay. Cell motility and invasiveness were assayed by Matrigel migration and invasion assay. Flow cytometry and western blot analysis were used to detect cell apoptosis, cell cycle and signaling pathway. Results: The results demonstrated that apigenin suppressed proliferation and inhibited the migration and invasion potential of T24 bladder cancer cells in a dose- and time-dependent manner, which was associated with induced G2/M Phase cell cycle arrest and apoptosis. The mechanism of action is like to involve PI3K/Akt pathway and Bcl-2 family proteins. Apigenin increased caspase-3 activity and PARP cleavage, indicating that apigenin induced apoptosis in a caspase-dependent way. Conclusions: These findings suggest that apigenin may be an effective way for treating human bladder cancer.

via Cancer Cell International

BAD overexpression inhibits cell growth and induces apoptosis via mitochondrial-dependent pathway in non-small cell lung cancer

Background: The pro-apoptotic Bcl-2 protein BAD initiated apoptosis in human cells and has been identified as a prognostic marker in non-small cell lung cancer (NSCLC). In this study, we aimed to explore the functions of BAD in NSCLC. Methods: Overexpression of BAD was performed by transfecting different NSCLC cell lines with wild-type BAD. Cell proliferation, cell cycle, apoptosis, and invasion were characterized in vitro. Tumorigenicity was analyzed in vivo. Western blot was performed to determine the effects of BAD overexpression on the Bcl-2 family proteins and apoptosis-related proteins. Results: Overexpression of BAD significantly inhibited cell proliferation in H1299, H292, and SPC-A1 but not in SK-MES-1 and H460 cell lines in vitro. BAD overexpression also reduced the tumorigenicity of H1299/SPC-A1 cell in vivo. However, no appreciable effects on cell cycle distribution and invasion were observed in all these cell lines. BAD overexpression also induced apoptosis in all cell types, in which process expression of mitochondrial cytochrom c (cyto-c) and caspase 3 were increased, whereas Bcl-xl, Bcl-2, Bax and caspase 8 expressions did not changed. These findings indicated that a mitochondrial pathway, in which process cyto-c was released from mitochondrial to activate caspase 3, was involved in BAD overexpression-mediated apoptosis. Conclusions: Our data suggested that increased expression of BAD enhance apoptosis and has negative influence on cell proliferation and tumor growth in NSCLC. Bad is a new potential target for tumor interventions.

via Cancer Cell International

Mediastinal mature teratoma with complex rupture into the lung, bronchus and skin: a case report

Mature teratoma is the most common primary germ cell tumor in the mediastinum. On rare occasions, cystic teratomas rupture in adjacent structures, such as pleural space, pericardium, lung or tracheobronchial tree. We present a case of a mediastinal mature cystic teratoma in 16-year-old female with complex rupture into the lung, bronchus and skin. Mature mediastinal teratoma fistulized to the skin has not been previously described.

via World Journal of Surgical Oncology