International Journal of Cancer Therapy and Oncology
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Bronchial carcinoid with massive ossification: A case report and review of literature
Get PDFWe report a case of a 47-year-old male with unexplained fatigue, shortness of breath, fever, chronic cough, and weight loss of over 12 pounds over a 3 months period. Chest x-ray revealed complete opacification of the right hemithorax with collapse of the right middle and lower lung lobes and midline shift towards the right. A CT scan with contrast showed a 6 cm mass arising from the right mainstem bronchus that was completely occluding the lumen, causing right lung atelectasis. Histopathologic examination of the tumor revealed an atypical carcinoid tumor with massive ossification. This is a case report and review of the literature of the rare bronchial carcinoid demonstrating bone formation
Guanylyl Cyclase C as a tumor marker for detection of circulating tumor cells in the peripheral blood of colorectal cancer patients
Get PDFPurpose: Guanylyl cyclase C (GCC) is one of the most frequent tumor markers to detect the circulating tumor cells (CTCs) in peripheral blood of colorectal cancer (CRC) patients. It has been proposed as a new marker for the molecular staging of CRC. The level of GCC mRNA expression in peripheral blood of CRC patients was evaluated to explore its probable correlations with the clinicopathological features.Methods: Relative quantitative expression analysis of GCC mRNA was performed on 80 blood samples (40 patients and 40 normal) using the Real-time RT-PCR.Results: GCC mRNA expression was detected in 70% of the CRC blood samples. The level of GCC mRNA expression in peripheral blood of patients was significantly higher than that in the normal cases (p = 0.031). Moreover, there was a significant correlation between the GCC copy number and advanced stages of tumor (p = 0.041). Furthermore, we have observed a significant correlation between tumor sizes and GCC copy numbers (p = 0.050).Conclusion: GCC can be a useful marker not only for detection of CTCs in CRC blood samples, but also for the molecular staging of colorectal cancer.
Extra-abdominal desmoid tumor: A case report
Get PDFDesmoid tumor represents a rare monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Although histologically benign, desmoids are locally invasive and associated with a high local recurrence rate, but lack of metastatic potential. Many issues regarding the optimal treatment of patients with desmoids remain controversial. Surgical resection and radiotherapy are standard treatment options for these patients. Due to heterogeneity of the biological behavior of desmoids, including long periods of stable disease or even spontaneous regression, treatment needs to be individualized to optimize local tumor control and preserve patient's quality of life. Therapeutic approaches to the treatment of recurrent or unresectable desmoid tumors comprise anti-hormonal therapy, non-steroidal anti-inflammatory drugs, classic chemotherapy regimens and tyrosine kinase inhibitor, with highly variable results. It has not yet been possible to establish an optimal therapy protocol for this disease. In this case report we present our experience with the treatment of recurrent extra-abdominal desmoid tumor.
Pyruvate dehydrogenase kinase inhibition: Reversing the Warburg effect in cancer therapy
Get PDFThe poor efficacy of many cancer chemotherapeutics, which are often non-selective and highly toxic, is attributable to the remarkable heterogeneity and adaptability of cancer cells. The Warburg effect describes the up regulation of glycolysis as the main source of adenosine 5’-triphosphate in cancer cells, even under normoxic conditions, and is a unique metabolic phenotype of cancer cells. Mitochondrial suppression is also observed which may be implicated in apoptotic suppression and increased funneling of respiratory substrates to anabolic processes, conferring a survival advantage. The mitochondrial pyruvate dehydrogenase complex is subject to meticulous regulation, chiefly by pyruvate dehydrogenase kinase. At the interface between glycolysis and the tricarboxylic acid cycle, the pyruvate dehydrogenase complex functions as a metabolic gatekeeper in determining the fate of glucose, making pyruvate dehydrogenase kinase an attractive candidate in a bid to reverse the Warburg effect in cancer cells. The small pyruvate dehydrogenase kinase inhibitor dichloroacetate has, historically, been used in conditions associated with lactic acidosis but has since gained substantial interest as a potential cancer chemotherapeutic. This review considers the Warburg effect as a unique phenotype of cancer cells in-line with the history of and current approaches to cancer therapies based on pyruvate dehydrogenase kinase inhibition with particular reference to dichloroacetate and its derivatives
Borderline phyllodes tumor of breast in a premenarchal girl: A relatively common tumor at an uncommon age
Get PDFPhyllodes tumors are relatively rare breast lesions that usually occur in the age group of 35 ‒ 55 years. It is a very rare diagnosis in young girls, particularly at prepubertal age. Because of the uncommon nature of this tumor in children, it may be misdiagnosed leading to inappropriate management. We report a case of a 9–year-old girl who was diagnosed as a case of borderline phyllodes tumor left breast. Simple mastectomy without axillary staging was performed. She has recovered well and is on follow up
Lunasin—a multifunctional anticancer peptide from soybean
Get PDFLunasin is a bioactive peptide that was originally isolated from soybean and has since been shown to have a number of biological activities, including both cancer chemopreventive and therapeutic activities. Our recent focus has been on determining the range of cancer types that lunasin can affect and the mechanism of action against specific cancers. We recently found that lunasin has significant therapeutic activity against non-small cell lung cancer (NSCLC) both in vitro and in vivo. Mechanistic studies using lunasin-sensitive and lunasin-resistant NSCLC cell lines revealed the lunasin blocks cell proliferation by inhibiting cell cycle progression at the G1/S phase interface and that this inhibition was associated with reduced Akt signaling. In addition, we found that these effects were linked to the inhibition of integrin signaling through αv-containing integrins. Our results provide strong support for the hypothesis that direct effects on integrin signaling represent a major mode of action responsible for lunasin’s anticancer activity.
The impact of homocysteine level on methotrexate induced neurotoxicity in children treated with St. Jude total XV acute lymphoblastic leukemia protocol
Get PDFPurpose: Methotrexate (MTX) is an antimetabolite that is routinely used in the treatment of hematological malignancies and during its metabolism leads to hyperhomocysteinemia that is associated with neurotoxicity. The purpose of this prospective study is to determine whether the increase in plasma homocysteine (Hcy) concentration is related to MTX-induced neurotoxicity.Methods: We investigated these changes for both newly diagnosed acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) pediatric patients treated at the National Cancer Institute, Egypt. They were treated according to St. Jude total XV protocol to receive 2.5 or 5 g/m2 MTX as a phase of consolidation and were selected between October 2009 and January 2010.Results: Twenty-nine patients were analyzed, M/F: 20/9, the mean age was 8 +/- 4.4 years. Hcy level above 15 µmol/L was considered positive. Hcy levels mean at diagnosis, pre 1st HD MTX, post 1st HDMTX, Pre 2nd HDMTX, Post 2nd HDMTX were 12.10 µmol/L ± 4.17, 6.90 µmol/L ± 3.02, 17.59 µmol/L ± 6.00, 7.21 µmol/L ± 2.73 and 13.74 µmol/L ± 4.75 respectively. Seventeen patients (58%) had features suggestive of neurotoxicity. Positive Hcy levels were associated with neurotoxicity p = 0.05, higher HDMTX 5 g/m2 P= 0.023. A highly significant relation was found between initial Hcy level at diagnosis and final Hcy level p = 0.001; the same as between Hcy level Post 1st HDMTX and that Post 2nd HDMTX with p = 0.006.Conclusion: plasma Hcy concentration was significantly elevated after HDMTX administration and this elevation is associated with the observed neurotoxicity. Whether the elevation in Hcy concentration can prove an informative biomarker for neurotoxicity requires additional testing with other MTX regimens
Concurrent versus sequential chemoradiotherapy for locally advanced resectable hypopharyngeal carcinoma
Get PDFPurpose: Both concurrent and sequential chemoradiotherapy have been reported to be good alternatives to total laryngectomy in patients with locally advanced hypopharyngeal cancer. We retrospectively reviewed the results of concurrent vs sequential chemoradiotherapy in two institutions for treatment of locally advanced resectable hypopharyngeal cancer in an effort to optimize future laryngeal preservation treatment.Methods: Seventy-two patients with locally advanced resectable hypopharyngeal squamous cell carcinoma were reviewed. Arm I included 38 patients treated by concurrent chemoradiotherapy (CCRT) while arm II included 34 patients received sequential chemoradiotherapy. In arm I patients received CCRT of cisplatin 100 mg/m2 d1, 22 of radiotherapy at dose of 65 Gy/1.8 - 2 Gy/f, 5 days/week. Patients in arm II received 2 cycles of induction chemotherapy consisted of 5 - fluorouracil 1000 mg/m2 on d1 - 4 on 24 h continuous infusion plus cisplatin 100 mg/m2 d1; cycle was repeated every 3 weeks followed by radiotherapy as in arm I.Results: Demographic data were balanced in both arms. The median age was 50 and 48 years in arm I and II respectively. There was male predominance in both arms. Most of the patients were of ECOGPS of 1and of stage III. No recorded deaths due to treatment toxicities .But as expected CCRT was associated with higher toxicity. In order of frequency; mucositis, anemia were higher in arm I. Significantly higher response rate was observed in arm I (p = 0.04).Three-year survival rates were 74% in arm I and 67.9% in arm II with no significant difference (p = 0.074) but 3 - year PFS rate was significantly higher in arm I (52.6% vs. 47%) (p = 0.03). Laryngeal - preservation rate was 78% in arm I vs. 56% in arm II with significant difference.Conclusion: There was higher benefit of concurrent chemo-radiotherapy over sequential chemoradiotherapy. However, larger number of patients and prospective randomized trials are needed to confirm our findings. New strategies that improve organ preservation with less toxicity are needed
Hyaluronan-mediated ferric oxide nanoparticles causes apoptosis of CD44 expressing head and neck squamous cell carcinoma cells
Get PDFPurpose: To eliminate CD44, a putative cancer stem cell (CSC) marker, overexpressing head and neck squamous cell carcinoma (HNSCC) cells by using hyaluronan-conjugated, dextran-coated super paramagnetic iron oxide nanoparticles (HA-DESPIONs), in conjunction with induced heat produced by exposure to an alternating magnetic field (AMF).Methods: An AMF generator was constructed by means of a solenoid coil and an impedance circuit driven by a power amplifier. A signal generator produced a small sinusoidal signal of 130 kHz that was then amplified to 9 A (peak to peak value) to generate an AMF of approximately 10 kA/m (12.6 mT) at the center of a coil. The heat generating effect of the AMF generator was tested via several kinetic and dose-dependent bulk heating experiments by exposing readily available magnetic nanoparticles to AMF. For elimination of CD44 population, UT-SCC-14 cells were exposed to either targeted HA-DESPIONs or non-targeted DESPIONs at a concentration 200 μg/ml and exposed to AMF for 30 minutes. Cells were processed after 24 hours for flow cytometry based analysis of apoptosis.Results: Magnetic nanoparticles caused a concentration-dependent bulk heating effect in response to AMF resulting in a significant temperature rise. Following the exposure to AMF, non-conjugated DESPIONs were unable to induce targeted hyperthermia and hence had no effect on CD44 cell death in HNSCC cells. However, there was a significant cell death in the CD44 population treated with HA-DESPIONs and exposed to AMF. This effect was only obeserved when the magnetic field was turned on.Conclusion: Bulk heating experiments concluded that a simple AMF generator was able to activate magnetic nanoparticles and flow cytometry demonstrated that HA- DESPIONs were able to cause apoptosis in UT-SCC-14 cells that express CD44.This may be a promising strategy to specifically target cancer stem cells (CSCs) for the treatment of HNSCC
Dose-volume consistency and radiobiological characterization between prostate IMRT and VMAT plans
Get PDFPurpose: Dose-volume consistency of the planning target volume (PTV) and rectum for the prostate intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were evaluated and compared. Dependences of radiobiological parameters of the prostate and rectum on the PTV and rectal volume were also investigated.Methods: From 40 prostate IMRT and 50 VMAT patients treated with the same prescription (78 Gy per 39 fractions) and dose-volume criteria in the inverse planning, the prostate tumour control probability (TCP), rectal equivalent uniform dose (EUD) and rectal normal tissue complication probability (NTCP) were calculated. The dose-volume consistency of the PTV and rectum, demonstrating the variability of dose-volume histogram (DVH) among patients, was defined and calculated as per the deviation between the corresponding and mean DVH.Results: For the IMRT plans, the prostate TCP was found increasing with the PTV with a rate equal to 1.05 × 10-3 % cm-3, which was lower than 1.11 × 10-3 % cm-3 for the VMAT plans. Both the rectal EUD and rectal NTCP were found decreasing with the rectal volume. The decrease rates for the IMRT plans (EUD = 0.47 × 10-3 Gy cm-3 and NTCP = 3.94 × 10-2 % cm-3) were higher than those for the VMAT (EUD = 0.28 × 10-3 Gy cm-3 and NTCP = 2.61 × 10-2 % cm-3).Conclusion: For the dose-volume consistency, small prostate TCP variation could be achieved by decreasing the dose-volume variability among the IMRT and VMAT plans. However, dependences of the rectal EUD and rectal NTCP on the dose-volume variability were not significant. It is concluded that maintaining a good dose-volume consistency in prostate plans can decrease the prostate TCP variation among the IMRT and VMAT patients. However, dose-volume variability is not affected by variations of the rectal EUD and rectal NTCP.