Non-Hodgkin lymphoma of the cauda equina: a rare entity.

Primary involvement of the spinal cord by non-Hodgkin lymphoma is exceptionally rare. We report one such case in a 46-year-old gentleman which was successfully treated with surgery and adjuvant chemotherapy.

Orbital metastasis from thyroid cancer: a case report and review of the literature.

BACKGROUND: Differentiated thyroid cancer (DTC) is generally associated with an excellent prognosis. However up to 20% of DTC patients have disease events during subsequent follow-up; rarely patients present an aggressive disease with distant metastases (DM), mainly in the lung and bone. Metastases at unusual sites may also occur, generally in patients with disseminated disease. Orbital localization is rare and only few cases have been described so far. CASE DESCRIPTION: A 36 years-old man, treated with chemo and radiotherapy during childhood for non-Hodgkin lymphoma, was referred for suspicious lymph node (LN) and multiple lung metastases. Total thyroidectomy and latero-cervical (LC) lymphadenectomy were performed: papillary thyroid cancer (PTC), 25 mm, 11/17 LN metastases; pT2N1bM1. Post-treatment total body scan with I-131 showed LN and lung uptake. Eighteen months from diagnosis he presented progressive diplopia, proptosis and right exophthalmos due to an 18 mm orbital metastasis. Hence, due to I-131 refractoriness for structural disease progression despite I-131 therapy, he started therapy with Lenvatinib for 6 months, with initial partial response followed by disease progression, and then with Cabozantinib, which he stopped after 6 months for adverse events and disease progression after therapy reduction. Currently, the patient is receiving Lenvatinib, rechallenge therapy, with disease stabilization and biochemical response. Molecular analysis, performed on both primary and relapsed tumor didn't show any significant pathogenic alteration. CONCLUSIONS: This case of DTC with an unusual metastasis in the orbit, may suggest that patient's exposure to chemo- and radiotherapy during pediatric age might have played a role in the subsequent development of this unusually aggressive tumor, reinforcing the recommendation of long-term and intensive follow-up of these patients.

RADIATION AND CHEMORADIATION THERAPY FOR I STAGE INTERMEDIATE AND HIGH/INTERMEDIATE ENDOMETRIAL CANCER - DESCRIPTIVE ANALYSIS. / PROMENEVA TA KhIMIOPROMENEVA TERAPIIa U LIKUVANNI RAKU ENDOMETRIIa I STADIÏ PROMIZhNOÏ TA VYSOKOÏ GRUP RYZYKU -DESKRYPTYVNYI ANALIZ.

INTRODUCTION: Endometrial cancer ranks the third place in prevalence among all cancers in Ukraine. The surgicaltreatment and subsequent adjuvant treatment is planned according to the patient's risk group. The choice of radi-ation therapy and the need to add chemotherapy determines the level of recurrence-free survival. OBJECTIVE: The aim of the study was to analyze the database of treated patients in National Cancer Institute, with Istage endometrial cancer intermediate and high-intermediate group; determination of the most frequent choice ofradiation treatment in accordance with the risk group of patients with a hysterectomy with salpingo-oophorectomyfor further observation and evaluation of diseasefree survival. MATERIALS AND METHODS: Retrospective was analysed 245 patients with high and intermediate risk groups with stageI endometrial cancer. The exclusion criteria were: low-risk patients, stages II-IV and non-endometrioid histologi-cal variant. RESULTS: According to the analysis, there were 122/245 (49.8 %) patients of high risk group, 123/245 (50.2 %) ofintermediate risk group. High-risk patients underwent external beam therapy and brychytherapy, supplemented bychemotherapy in 5.8 % of cases (7 patients), brachytherapy with external beam therapy was performed in 58.2 % ofcases (71 patients), brachytherapy - in 8.1 % of cases (10 patients), external beam therapy was performed in 27.9 %cases. Intermediate and high-intermediate risk patients were distributed as follows: brachytherapy was performedin 41.5 % of cases (51 patients), brachytherapy with external beam therapy - 54.5 % (67 patients), external beamtherapy was performed in 5 patients. CONCLUSION: Brachytherapy is available for patients with intermediate risk endometrial cancer and external beamtherapy with possible addition of brachytherapy is recommended for high-intermediate and high-risk groups, espe-cially in patients with lymphatic vascular involvement. All patients are monitored for further assessment of recur-rence-free survival.

CEA, EpCAM, αvß6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy.

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvß6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvß6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvß6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.

Relationship Between Sarcopenia and Prognosis in Patient With Concurrent Chemo-Radiation Therapy for Esophageal Cancer.

Background: Sarcopenia, defined as skeletal muscle loss, has been known as a poor prognosis factor in various malignant diseases The aim of this study is to investigate the effect of sarcopenia on prognosis in patients with esophageal cancer who received concurrent chemo- and radiotherapy (CCRT). Methods: We retrospectively collected clinical data of 287 patients with esophageal cancer who were treated by definite CCRT at Gangnam Severance and Severance hospital from August 2005 to December 2014. The cross-sectional area of muscle at the level of the third lumbar vertebra was measured using pre- and post-CCRT computed tomography images. Sarcopenia was defined as skeletal muscle index <49 cm2/m2 for men and of <31 cm2/m2 for women by Korean-specific cutoffs. Overall survival (OS) and progression free survival (PFS) were analyzed according to sarcopenia. Results: Sarcopenia identified before CCRT did not affect OS and PFS. However, patients with post-CCRT sarcopenia showed shorter OS and PFS than patients without it (median OS: 73 months vs. 28 months; median PFS: 34 months vs. 25 months, respectively). Post-CCRT sarcopenia was an independent prognostic factor of poor OS (hazards ratio: 1.697; 95% confidence interval: 1.036-2.780; P = 0.036). In multivariate analysis, male sex (P = 0.004) and presence of CCRT-related complications, such as esophagitis or general weakness were significantly associated with post-CCRT sarcopenia (P = 0.016). Conclusions: Sarcopenia after CCRT can be a useful predictor for long-term prognosis in patients with esophageal cancer. To control CCRT-related complications may be important to prevent skeletal muscle loss during CCRT.

LINC00958-MYC positive feedback loop modulates resistance of head and neck squamous cell carcinoma cells to chemo- and radiotherapy in vitro.

BACKGROUND: Aberrant long non-coding RNA (lncRNA) expression contributes cancer development and resistance to therapy. This study first assessed expression of lncRNA LINC00958 in a variety of human cancers using GEPIA database data and then associated it with prognosis of head and neck squamous cell carcinoma (HNSCC) and investigated LINC00958 interaction with c-Myc and the c-Myc-related gene interplay in HNSCC cells. MATERIALS AND METHODS: A cohort of 48 HNSCC vs normal tissues was collected for qRT-PCR analysis of LINC00958 and c-Myc expression and statistical analyses. HNSCC cell lines were subjected to transfection with LINC00958 and c-Myc siRNAs or cDNA and their negative control siRNA or empty vector for qRT-PCR, Western blot, cell viability, colony formation, luciferase reporter, chromatin immunoprecipitation, and RNA immunoprecipitation assays. RESULTS: The data showed that LINC00958 expression was upregulated in HNSCC tissues and cell lines, upregulation of which was associated with poor tumor differentiation, advanced tumor stage, and shorter overall survival of patients. In vitro, LINC00958 expression induced HNSCC cell viability and colony formation, whereas knockdown of LINC00958 expression enhanced HNSCC cell sensitivity to ionizing radiation and cisplatin treatment. Mechanistically, LINC00958 is a direct target of c-Myc and can enhance the transcriptional activity of c-Myc, thus to form a positive feedback gene network in HNSCC cells, and in turn to modulate HNSCC cell resistance to chemo- and radiotherapy. CONCLUSION: This study demonstrated the LINC00958 interplay with c-Myc as a feedback loop facilitated HNSCC development and resistance to chemo- and radiotherapy. Targeting of such a network could be further evaluated as a novel therapeutic strategy for HNSCC patients.

DNA repair in cancer initiation, progression, and therapy-a double-edged sword.

Genomic and mitochondrial DNA molecules are exposed continuously for a damaging activity of chemical, physical, and internal genotoxicants. When DNA repair machinery is not working efficiently, the generation of DNA lesions and mutations leads to carcinogenic transformation. The high number of mutation going up to 105 per cell was recognized as a driving force of oncogenesis. Moreover, a high activity of DNA repair genes was hypothesized as a predisposition to metastasis. DNA repair potential has to be taken into account attempting to chemo- and/or radiotherapy. A low activity of DNA repair genes makes tumor cells more sensitive to therapy, but on the other hand, non-tumor cells getting lesions could form second primary cancer. Contrary, high activity of DNA repair genes counteracts attempted therapy. It means an individualized therapy based on recognition of DNA repair potential is recommended.

Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy.

PURPOSE: Intraoperative identification of rectal cancer (RC) can be challenging, especially because of fibrosis after treatment with preoperative chemo- and radiotherapy (CRT). Tumor-targeted fluorescence imaging can enhance the contrast between tumor and normal tissue during surgery. Promising targets for RC imaging are carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM) and the tyrosine-kinase receptor Met (c-Met). The effect of CRT on their expression determines their applicability for imaging. Therefore, we investigated whether CRT modifies expression patterns in tumors, lymph node (LN) metastases and adjacent normal rectal tissues. PATIENTS AND METHODS: Preoperative biopsies, primary tumor specimens and metastatic LNs were collected from 38 RC patients who did not receive CRT (cohort 1) and 34 patients who did (cohort 2). CEA, EpCAM and c-Met expression was determined using immunohistochemical staining and was semiquantified by a total immunostaining score (TIS), consisting of the percentage and intensity of stained tumor cells (0-12). RESULTS: In both cohorts CEA, EpCAM and c-Met were significantly highly expressed in >60% of tumor tissues compared with adjacent normal epithelium (T/N ratio, P<0.01). EpCAM showed the most homogenous expression in tumors, whereas CEA showed the highest T/N ratio. Most importantly, CEA and EpCAM expression did not significantly change in normal or neoplastic RC tissue after CRT, whereas levels of c-Met changed (P=0.02). Tissues of eight patients with a pathological complete response after CRT showed expression of all biomarkers with TIS close to normal epithelium. CONCLUSION: Histological evaluation shows that CEA, EpCAM and c-Met are suitable targets for RC imaging, because all three are significantly enhanced in cancer tissue from primary tumors or LN metastases compared with normal adjacent tissue. Furthermore, the expression of CEA and EpCAM is not significantly changed after CRT. These data underscore the applicability of c-Met and especially, CEA and EpCAM as targets for image-guided RC surgery, both before and after CRT.

Hypoxia-responsive lipid-poly-(hypoxic radiosensitized polyprodrug) nanoparticles for glioma chemo- and radiotherapy.

Treatment of malignant glioma is a challenge facing cancer therapy. In addition to surgery, and chemotherapy, radiotherapy (RT) is one of the most effective modalities of glioma treatment. However, there are two crucial challenges for RT facing malignant glioma therapy: first, gliomas are known to be resistant to radiation due to their intratumoral hypoxia; second, radiosensitizers may exhibit a lack of target specificity, which may cause a lower concentration of radiosensitizers in tumors and toxic side effects in normal tissues. Thus, novel angiopep-2-lipid-poly-(metronidazoles)n (ALP-(MIs)n) hypoxic radiosensitizer-polyprodrug nanoparticles (NPs) were designed to enhance the radiosensitizing effect on gliomas. Methods: In this study, different degrees and biodegradabilites of hypoxic radiosensitizer MIs-based polyprodrug (P-(MIs)n) were synthesized as a hydrophobic core. P-(MIs)n were mixed with DSPE-PEG2000, angiopep-2-DSPE-PEG2000 and lecithin to self-assemble ALP-(MIs)n through a single-step nanoprecipitation method. The ALP-(MIs)n encapsulate doxorubicin (DOX) (ALP-(MIs)n/DOX) and provoke the release of DOX under hypoxic conditions for glioma chemo- and radiotherapy. In vivo glioma targeting was tested in an orthotopic glioma using live animal fluorescence/bioluminescence imaging. The effect on sensitization to RT of ALP-(MIs)n and the combination of chemotherapy and RT of ALP-(MIs)n/DOX for glioma treatment were also investigated both in vitro and in vivo. Results: ALP-(MIs)n/DOX effectively accumulated in gliomas and could reach the hypoxic glioma site after systemic in vivo administration. These ALP-(MIs)n showed a significant radiosensitizing effect on gliomas and realized combination chemotherapy and RT for glioma treatment both in vitro and in vivo. Conclusions: In summary, we constructed a lipid-poly-(hypoxic radiosensitized polyprodrug) nanoparticles for enhancing the RT sensitivity of gliomas and achieving the combination of radiation and chemotherapy for gliomas.

Malignant pleural mesothelioma with lacrimal gland metastasis.

PURPOSE: To describe a rare clinical case of biopsy-proven metastatic mesothelioma of the lacrimal gland which responded well to chemo and radiation therapy. METHODS: Interventional case report. RESULTS: A 55-year-old woman with an untreated malignant biopsy-proven pleural mesothelioma presented with right proptosis, diplopia and hypoglobus. Magnetic resonance imaging showed an aggressive lacrimal gland tumour with bony erosion. A biopsy concluded a diagnosis of metastatic mesothelioma of the lacrimal gland. Her lacrimal and lung tumours showed a marked regression following palliative chemo (carboplatin) and radiation therapy. CONCLUSIONS: Malignant pleural mesothelioma may metastasize to the orbit, including the lacrimal gland. A combined chemo and radiation therapy may reduce the size of the metastatic and primary tumour.

In vivo antitumor potential of Ipomoea pes-caprae on melanoma cancer.

BACKGROUND: The incidence of skin cancers is rising gradually. The treatment of melanoma is also necessary to prevent the spread of cancer to other body organs. Scientific literatures have not documented any evidence of the antitumor potential of Ipomoea pes-caprae on melanoma. AIM OF THE STUDY: Explore in vivo antitumor potential of I. pes-caprae on melanoma cancer. MATERIALS AND METHODS: Petroleum ether (60°C-80°C), methanolic and aqueous extracts, and swaras prepared from the whole herb of I. pes-caprae were assessed for their antitumor activity. The extracts and swaras at doses of 25 and 50 mg/kg b. wt. were administered intraperitoneal along with chemo and radiotherapy for 40 days for exploring antitumor activity against melanoma cancer (B16F10) in male C57BL mice. The results obtained from tumor volume, and histopathological studies were compared with the control and dacarbazine used as a standard. RESULTS: Antitumor effect of I. pes-caprae extracts and swaras on melanoma cancer was found to be significant (P < 0.01) compared to normal control. The tumor volume inhibition against tumor-bearing mice, although differed from each other, was concentration dependent. Administration of plant extracts and swaras from the day 1 since tumor inducted. The induction of tumor was found delayed by 10-15 days and the tumor volume on the day 40 was similar to the Dacarbazine treatment used as a standard. CONCLUSION: The results obtained from the tumor volume and histopathological studies clearly revealed the antitumor potential of I. pes-caprae on melanoma cancer.

[From poly(ADP-ribose) discovery to PARP inhibitors in cancer therapy]. / De la découverte du poly(ADP-ribose) aux inhibiteurs PARP en thérapie du cancer.

Poly(ADP-ribosyl)ation is a post-translational modification catalyzed by poly(ADP-ribose) polymerases. PARP-1 is a molecular sensor of DNA breaks, playing a key role in the spatial and temporal organization of their repair, contributing to the maintenance of genome integrity and cell survival. The fact that PARP inhibition impairs efficacy of break repair has been exploited as anticancer strategies to potentiate the cytotoxicity of anticancer drugs and radiotherapy. Numerous clinical trials based on this innovative approach are in progress. PARP inhibition has also proved to be exquisitely efficient to kill tumour cells deficient in double strand break repair by homologous recombination, such as cells mutated for the breast cancer early onset genes BRCA1 or BRCA2, by synthetic lethality. Several phase III clinical trials are in progress for the treatment of breast and ovarian cancers with BRCA mutations and the PARP inhibitor olaparib has just been approved for advanced ovarian cancers with germline BRCA mutation. This review recapitulates the history from the discovery of poly(ADP-ribosyl)ation reaction to the promising therapeutic applications of its inhibition in innovating anticancer strategies. Benefits, hopes and obstacles are discussed.

New possibilities in hepatocellular carcinoma treatment.

Hepatocellular carcinoma diagnosis and treatment has witnessed many major changes and challenges in the past two decades. Increasing incidence of HCC has introduced new monitoring systems and increased the efficacy of screening tests, as well as prognosis of the disease, including the staging system, serological testing and diagnostic imaging. Moreover, surgical resection, liver transplantation and herbal therapy have improved treatment. The most encouraging specific serological marker for HCC is alpha fetoprotein (AFP), which, along with ultrasonography, has improved earlier detection of HCC. Most recently, circulating tumor cell measurement has emerged as a promising tool for the prognosis of HCC. Herbal drugs and herbal composite formula drugs are promising towards the prevention of invasion and proliferation of tumor cells. Chemotherapeutic agents, such as sorafenib, bevacizumab and erlotinib, which target growth factor receptors in signaling pathways, are also used as HCC treatments. Furthermore, radiotherapy is employed in the treatment of unresectable tumors. The present report provides an analysis of the above parameters in the management of HCC.