Krebswissenschaft und -therapie

Introduction: Breast cancer incidence is rising in our country and most of them are diagnosed at advanced stage. Triple negative subgroup carries dismal prognosis and lacks effective targeted treatment. With this study we have attempted to analyze clinical profile of triple negative breast cancer patient in Jharkhand.
Method: The study was done at HCG; Ranchi from January 2012 to January 2017. All histologically confirmed breast cancer patients were retrospectively included in the study. According to their receptor status they were divided into triple negative subgroup and other group. Their clinic-pathological characteristics and demographic details were compared.
Result: Triple negative subgroup accounts for 1/3rd of total breast cancer patient in Jharkhand. 41% of total tribal breast cancer patients in Jharkhand are triple negative. Most common stage at presentation in both group is stage III.
Conclusion: Effective cancer screening programs and cancer registries are required for adequate planning and execution of cancer programs. Further larger population based studies to study the genetic predisposition of tribal population towards triple negative subgroup.

Oral squamous cell carcinoma (OSCC) is the most prevalent cancer in Indian subcontinent with high recurrence rate, aggressive metastasis, and poor prognosis. The potential risk-factors for OSCC are tobacco smoking, alcohol intake, and persistent infection of oncogenic human papillomaviruses (HR-HPVs). HPV-positive OSCCs show distinct genetic and epigenetic changes along with distinct clinical, epidemiological and molecular characteristics. Recently, with the accumulation of large amount of genomic and epigenomic data, there is an increasing focus on epigenetic alterations playing key roles in cancer pathogenesis. Non-coding RNAs, especially the small noncoding RNAs (sncRNAs) have gained attention since they have been demonstrated to fine tune transcription via alterations in the epigenetic landscape. There are ample evidences supporting the role of small non-coding RNAs such as miRNAs and piRNAs in development and disease including cancers. PIWI-interacting RNAs (piRNAs), a class of sncRNAs are emerging players involved in transcription silencing. Its altered regulation is associated with the development of variety of tumors including oral carcinogenesis; however, their tumor specific roles are not fully understood. Therefore, identification and comprehensive characterization of oncogenic as well as tumor suppressive pi-RNAs and dissecting their roles in tumorigenesis is of great importance in the field of cancer biology. Furthermore, piRNAs may potentially serve as unique therapeutic targets and/or molecular markers for early detection and effective treatment of OSCC subtypes. In this mini review, we briefly summarize the emerging role of PIWI-RNAs in oral cancer.

Cancer cells change the properties of surrounding cells via secretion signaling. The effects of tumor communication were found to cause molecular alterations in peripheral blood mononuclear cells (PBMCs). These alterations could be applied in a blood-based test for cancer detection, especially with epithelial ovarian cancer (EOC). This cancer has less effective screening tools and nonspecific symptoms leading to high mortality rates in patients. Therefore, a novel biomarker for screening is required. A simulated model of cancer cell signaling was performed by the co-culture of normal PBMCs with ovarian cancer cell lines. Transcriptome analysis was then performed using RNA sequencing (RNA-seq). In addition, we retrieved expression microarray (GSE31682) data from GenBank and combined this expression data with the two groups of RNA-seq data using Connection Upand Down-Regulation Expression Analysis of Microarrays extension (CU-DREAMX). The most upregulated gene, GTPase IMAP family member eight (GIMAP8), was selected for validation by quantitative reverse transcription polymerase chain reaction in PBMCs from 16 ovarian cancer patients compared with 15 healthy controls. The GIMAP8 expression was significantly increased in ovarian cancer patients (p-value < 0.0001). Interestingly, there was high expression in all three cases of clear cell and four cases of serous adenocarcinoma. We determined that PBMCs changed their gene expression as a result of ovarian cancer cell signaling. Furthermore, the expression level changes in GIMAP8 could be applied for cancer screening, diagnosis, and treatment monitoring purposes.

Background: The treatment of nasopharyngeal carcinoma (NPC) consists of radiotherapy alone (stage I) or radiotherapy concomitant with chemotherapy (stage II-V). Acute side effects management forms a major challenge for practitioners. Substantial literature is available from endemic areas, whereas data from Europe is scarce. This study examines clinical characteristics, therapeutic results, acute and late side effects of patients treated at the Jules Bordet Institute.
Materials and Methods: Twenty-two consecutive non-metastatic NPC patients treated between May 2012 and September 2015 were retrospectively analyzed. All patients were treated by Intensity Modulated Radiation Therapy (IMRT) with or without chemotherapy (CT).
Results: Thirteen patients have North-African ancestry while nine are of European origin. Seventy-three percent had a non-keratinizing carcinoma and 90% had an advanced stage disease (III-IVb). Ninety-five percent of the patients received concomitant CT. After a median follow-up time of 31 months, overall survival was 77%. Local, regional and distant control rates were 95%, 86% and 73%. Main acute grade 3 toxicities were swallowing disorders (91%), vomiting (82%), oropharyngeal mucositis (64%) and dermatitis (23%). Only one patient developed grade 4 dermatitis, requiring treatment discontinuation in the sixth week. In the seventh week of treatment, 86% of the patients had lost more than 10% of their starting weight. Univariate analysis identified three factors driving the weight loss: grade 3 mucositis of the soft palate (p=0.027), vomiting (p=0.019) and pre-treatment dental extraction (p=0.006). In multivariate analysis, weight loss is only linked to dental extraction (p=0.042, Odds Ratio 1.62, [95% CI: 1.16-2.80]). Late toxicities were xerostomia (68%), auditory symptoms (55%), hypothyroidism (45%) and swallowing disorders (23%).
Conclusion: Our clinical characteristics outcome and toxicity are comparable to published data from endemic regions. Interestingly, weight loss of >10% is correlated to pre-treatment dental extraction. This finding should be confirmed and analyzed in a prospective manner.

Osteosarcoma is the most common bone tumour seen in the paediatric and adolescent age group. Most osteosarcomas are highly malignant tumours arising within the bone. Several markers for diagnosis and prognosis have been proposed in osteosarcoma namely, vascular endothelial growth factor (VEGF), bone alkaline phosphatase, osteocalcin. A new family of a protein known as Vasodilator-stimulated phosphoprotein, which is known to promote cell migration may also have a role in metastasis of osteosarcoma. So this study was planned to estimate the serum concentration of VASP in patients of osteosarcoma and to find the correlation of it with serum alkaline phosphatase and compare them with controls. Fifty patients attending the Orthopaedics clinics were selected for the study and were divided into two groups. Histopathologically confirmed cases of osteosarcoma (localized without metastasis) were included in Group I and age and sex matched twenty five patients with musculoskeletal pain in Group II as controls. Serum alkaline phosphatase levels and serum vasodilator-stimulated phosphoprotein (VASP) levels were estimated and the result was analysed using standard statistical methods. It has been found that serum VASP levels were significantly decreased and serum alkaline phosphatase levels were significantly raised in patients with osteosarcoma (Group I) as compared to the controls. Serum alkaline phosphatase levels showed a positive correlation with serum VASP levels in control, which got inverted in osteosarcoma cases. VASP, a member of ENA/VASP family, has been implicated in regulating key cellular functions (namely shape change, adhesion and migration) due to its ability to modify dynamic cytoskeleton. The negative correlation between VASP and ALP in osteosarcoma patients also supported the role of VASP in bone mineralization and tumorigenesis. So, VASP in osteosarcomas may lead to improved stratification of outcome and development of novel therapeutic modalities.

Introduction and Hypothesis: The current standard treatment for early breast cancer includes conservative surgery followed by whole breast radiotherapy (WBRT). Recent study findings show that most local recurrences are in the scar tissue area suggesting that whole-breast radiotherapy may not always be necessary. If the volume of breast tissue to be irradiated is limited, radiotherapy may be performed as intraoperative. Intraoperative radiotherapy could in principle substitute the currently used radiation course of external radiotherapy after breast-conserving surgery in selected cases.
Patients and Methods: Patients were enrolled at two center. Khatam Hospital (related to CRC1, SBMU2) patients were delivered intraoperative electron beam during surgery and Azar Clinic (related to CRC) patients received external beam radiotherapy after surgery. Suitable criteria was age>45 y, tumor size ≤ 3 cm, lymphnode negative. Though we included some patients 40-44 y and T=3-4 cm, N=0 and favorable biomarkers as Possible Group.
Results: We applied full dose electron beam intraoperative radiotherapy to 216 patients with early breast cancer and suitable for breast conserving surgery. Afterwards, we compared results with 323 patients with early breast cancer and external beam radiotherapy. Within 4 years for the invasive breast cancer patients, local recurrence was 2 (1.06%) and 1 (0.36%) and also, systemic recurrence was 1and 4 patients in the intraoperative and external radiotherapy groups, respectively. Mortality was 3 cancer related death and the other one, none cancer related death in the external radiotherapy patients. There was not any cancer related death for intraoperative radiotherapy patients.
Conclusion: Comparison of local recurrence in two groups (p-value: 0.335), via demonstrated that IOERT in contrast with EBRT had not inferiority however, it had superiority about systemic recurrence and death. In addition, we can transcend the boundaries of the definition, such as age, tumor size, histology. Invasive lobular carcinoma and DCIS with special characters could be one of these.