Loading

JSM Surgical Oncology and Research

Size In Breast Invasive Ductal Carcinoma Leads Changes in Important Biological Parameters

Short Communication | Open Access Volume 1 | Issue 2 |

  • 1. Department of Nuclear Medicine, University Hospital of Santiago de Compostela, Spain
+ Show More - Show Less
Corresponding Authors
Michel Herranz, Department of Nuclear Medicine, University Hospital of Santiago de Compostela, Travesia Choupana s/n. 15706, Santiago de Compostela, Spain, Tel: 34-636497150
Abstract

Introduction: We analyzed the behavior of certain clinical and biological aspects in breast invasive ductal carcinomas (IDC) when tumor size increased up to three centimeters

Material and Methods: We studied 627 women affected by IDC and aged between 29 and 88 years (median 62), classified into three groups: </ = 0.5 cm: 45; between 0.51 and 1 cm: 180 and 1.1 to 3 cm: 402 cases. The analyzed clinical and biological parameters were: axillary lymph node involvement (N), distant metastasis (M), immunohistochemical expression of estrogen receptors (ER), progesterone receptors (PgR), androgen receptors (AR), p53, Ki67, bcl2, and cytosolic concentrations of cathepsin D and hyaluronic acid (HA), as weel as the epidermal growth factor receptor (EGFR), HA, CD44v5 and CD44v6 in cell membranes.

Results: Tumors <1 cm showed no statistical differences among all analyzed parameters. Tumors with size range between 1.1 and 3 cm presented, compared with size less than or between 0.5 and 1 cm, higher concentrations of cathepsin D (p = 0.001) increased expression of p53 (p <0.0001), ki 67 (p <0.0001), CD44v5 (p: 0.008), axillary lymph node involvement (p <0.0001), distant metastasis (p = 0.026), and decreased expression of bcl2 (p: 0.057) and membrane HA (p: 0.051).

Conclusions: Our results suggest that it is from one cm in size when is evidenced in invasive ductal breast carcinomas certain clinical and biological properties source of increased proliferation and tumor aggressiveness.

Keywords

• Breast cancer
• Ductal Carcinoma

CITATION

Ruibal A, Aguiar P, Arias JI, Herranz M (2016) Size In Breast Invasive Ductal Carcinoma Leads Changes in Important Biological Parameters. JSM Surg Oncol Res 1(2): 1006.

INTRODUCTION

Size is a key factor in the progress of breast cancer, because many of its invasive-metastatic properties appear as size increases. In addition, with lymph node involvement (N) and distant metastasis (M), set the TNM classification, widely used in daily practice [1]. We know that T1a carcinomas (( 2-5 cm) [2]. In addition, tumors less (or equal) than 1 cm have a very low risk of recurrence, and disease-free survival in cases without axillary lymph node involvement reaches 92-96%, surviving up to 10 years 90% of patients. Numerous studies have demonstrated the prognostic value of tumor size, evidenced in stages 1 with other clinical and biological parameters such as age, lympho vascular invasion and high proliferation [3-6],

We wanted to analyze the impact of size on the biology of breast IDC tumors analyzing the behavior of certain clinical and biological when tumor size was increased up to three centimeters.

MATERIALS AND METHODS

The study group included 627 women with breast invasive ductal carcinonas (IDC) and aged between 29 and 88 years (61.3 +/- 10.3; median 62), from the Breast Pathology Unit of Hospital Monte Naranco Oviedo (Spain). Depending on the tumor size, patients were classified into three groups: 3 ng / mg prt.) and CD44v6 (> 6ng / mg prot.) Breast carcinoma tissue samples were obtained at the time of surgery. Immediately after surgical resection, samples were processed for pathological examination while the remainder tissue was washed with cold saline solution, divided in a liquots, rapidly transported on ice to the laboratory (-70º C) pending biochemical studies. The specimens obtained from neoplastic tissues were pulverized with a microdismembrator (Braun BiotechInternational, Melsungen, Germany) at -70º C and homogenized in TRIS-hydrochloride buffer (10 mM of TRIS, 1.5 mM of EDTA, 10% glycerol, 0.1% of monothioglycerol). Homogenates, kept at 4º C, were centrifuged at low speed (800 g for 10 min, at 4º C), and the supernatant was ultracentrifuged at 100.000 g for 60 min, at 4º C. We obtained a supernatant containing the cytosol and a precipitate with the membranes. Methods used were the following: CD44v6 and CD44v5 were assayed in cell surface membranes using an enzymoimmunoassay from Bender MedSystems (Vienna, Austria), epidermal growth factor receptor (EGFR) was assayed in cell surface membrane using a radiolig and method (ViennaLab, Austria), hyaluronic acid using a radiolig and method from Pharmacia (Sweden) and cathepsin D was assayed in cytosols using an immunoradiometric assays (CIS BioInternational. France). All results were referred to mg of protein measured by Bradford method [7]. Immunohistochemical expression was studied through the technique of tissue-matrix using Tissue Arrayer Device (Beecher Instruments, Sun Prairie, WI) to set up tissue blocks following conventional protocols [8]. The most representative areas were highlighted in the paraffin blocks and two pathologists performed case evaluation independently. Two selected 1-mm-diameter cylinders from two different areas were included in each case from the carcinomas as well as internal and external control areas. Each block was sectioned in 4 um and the immunohistochemical study was performed on 4 micron paraffin sections, using the Kit with universal secondary antibody that included a labelled-dextran polymer (DAKO EnVision Peroxidase/DAB; Glostrup. Denmark) to avoid false positive reaction due to endogenous biotin activity. Immunohistochemistry expression of Estrogen receptor (ER), progesterone receptor (PgR), androgen receptor (AR), Ki67, p53 and bcl2 were determined using mAbs ER/PR phramDx (clones 1D5 and ER-2-123 for ER and PgR1294 for the PR: Dako; Denmark), p53 (DO-7, Dako. Denmark), Ki67 (MIB-1, Dako; Denmark), bcl2 (124, Dako, Denmark) and androgen receptor (AR441, Dako; Denmark). ER and PgR were assessed according to the Allred score in negative (scores 0-2) and positive (score 3-8) and the thresholds of positivity for p53, Ki67 were 20% and 15 % respectively. AR were classified as positive or negative without any score, and bcl2 as negative (-: 30%).

Data obtained were evaluated using the SPSS 15.0 software for Windows (SPSS, Chicago, IL. USA). With the parameters that did not follow a normal distribution, values were presented as range, and median. We used the Chi square test with Yates correction, if necessary, for qualitative variables comparison and the Mann Whitney test for continuous ones. A p-value ≤ 0.05 was considered as statistically significant.

RESULTS

Analyzing the results, we found that tumors <1 cm showed no statistical differences among all analyzed parameters. However, tumors of size between 1.1 and 3 cm showed, versus those tumors size between 0.5 and 1 cm (Table 1) cathepsin D concentrations higher (p = 0.001), higher expression of p53 (p <0.0001), ki 67 (p <0.0001), CD44v5 (p: 0.008), axillary lymph node involvement (p <0.0001), distant metastasis (p = 0.026), and lower expression of bcl2 (p: 0.057) and HA membrane (p = 0.051).

Table1: Clinical-biological differences between breast invasive ductal carcinomas with sizes between 0.51 and 1 cm vs size between 1.1 and 3 cm.

Parameter

 

0,51-1 cm

   

1,1-3,0 cm

 

RANGE Median

RANGE Median

p

CATD*

31

1,6-126 (28,3)

294

1,5-1145 (45,2)

0,001

EGFR**

29

0,5-1030 (6,0)

278

0,1-2906 (4,7)

ns

HAc***

25

526-19074(3565)

236

591-430558(4642)

ns

HAcm***

16

449-4925 (2105)

117

50-6043 (1561)

0,051

ER+

 

147/180

327/402

 

ns

PgR+

 

112/180

223/402

 

ns

AR+

 

110/133

265/346

 

ns

p53+

 

13/149

71/370

<0.0001

 

ki67+

 

18/155

153/402

<0,0001

 

bcl2+

 

113/142

253/355

 

0,057

CD44v5+

 

14-Jun

86/110

 

0.008

CD44v6+

 

14-Apr

43/110

 

ns

N+

 

33/180

305/402

 

<0,0001

M+

 

6/180

36/402

 

0,026

*: pmol/mg prot.                                                                  

CATD: cathepsin D

**: fmol/mg prot.                                                               

***: ng/mg prot.

EGFR: Epidermal Growth Factor Receptor    N: lymph node involvement

M: distant metastasis; HAc: Cytosolic Hyaluronic Acid; HAcm: Cell Membrane Hyaluronic Acid

DISCUSSION

Results show significant clinical and biological changes when tumor size exceeds one centimeter, reflecting:

First, an increased tumor proliferation, as evidenced by the highest values of Ki67 [9]. We know that high K67is associated with higher nuclear grade, p53-positive and HER2-positive, being its value higher in triple negative than in other subtypes [10]; likewise it is an independent prognostic factor in invasive [11,12] and in situ carcinomas [13]. Some differences in Ki-67 in tumours of various receptor profiles have been described recently [14]. ER+/ Ki-67+ ratio can be used to differentiate invasive cancers from benign and proliferative breast tumours [15]. Second, an increased cell de-differentiation, reflected by lower concentrations of membrane hyaluronic acid, because we know that is inversely correlated with the histological grade and diploid [16]. Also we can find that the transition from HG1 to HG2 and from HG2 to HG3 was accompanied by a number of common features as global increase in size, greater number of tumor>2cm, decrease in membrane HA levels, increased cell proliferation (SF>7%) and a greater aneuploidy [17].

Third, amore invasive phenotype. We know that HA is an abundant extracellular matrix component and its synthesis is regulated by some growth factors (EGF, TGFbeta) and cytokines (IL 1beta). Increased synthesis of HA is often associated with malignancy in many different tumors including breast cancer [18] and likewise HA is involved in epithelia-mesenchimal transition (EMT) [19]. Increased HA production is able to stimulate the production of MMP2 and MMP9 leading to a more invasive phenotype in certain tumor cell lines [20]. CD44 is a transmembrane glycoprotein, widely expressed in almost all body cell types [21] and plays various functions in cell division, migration, adhesion, and signalling [22]. Its primary ligand is hyaluronic acid (HA). CD44 is an adhesion molecule and mediates the signal transduction of human epidermal growth factor receptor (HER) and other cell signalling pathways. We found increased expression of CD44v5 (> 3 ng / mg prot.) In Invasive ductal breast carcinomas (65.2%) vs DC in situ (25%) and the normal breast tissue (5.9%) [23]. We also found increased expression in tumors larger than 1 cm associated with the metastatic potential [24], with the highest expression of progesterone receptor and with tumor size> 2 cm [25]. In Invasive lobular carcinomas membranous staining of CD44v5 correlated with lymph node positive patients [26]. Also the concentration of soluble CD44v5 was associated with a greater capacity for dissemination [27]. We observed no difference in the expression of CD44v6 while XJ Wu et al., [28] describe a significant positive correlations between CD44v6 immuno positivity, tumour diameter and TNM stage. In relation to p53, we know that the expression of p53 and Ki67 are strong individual indicators of outcome [29]. TP53 mutations confer unfavourable prognosis in patients with Luminal A/B and TNBC tumors, while p53 immunopositivity may predict for trastuzumab benefit in the adjuvant setting [30]. Positive p53 status is associated with large tumors and lymph node metastases [31].

bcl2 is an interesting biological parameter in breast carcinomas. Immuno histo chemical expression of bcl2 in hormone-independent (ER and PgR negative) breast carcinomas is associated with greater axillary lymph node involvement and a greater number of deaths in the follow-up, being these data opposite to that observed in hormone-dependent tumors [32]. Also it is an independent predictor of outcome in basal-like triple negative breast cancers treated with adjuvant anthracyclinebased chemotherapy [33]. Significant and negative relations between bcl2 and Ki67 persisted during the progression of histological grade (HG), from HG1 to HG3, in invasive ductal carcinomas of the breast (IDC) <1 cm [34]. Bcl2/Ki67 combination phenotypes, together with PgR expression, can also refine luminal A cancers prognostic [35]. Ki67/BCL2 index correlated with shorter disease-free survival and overall survival in patients with early stage invasive ductal carcinoma (all p<0.05) [36]. Fourth, a greater invasive-metastatic ability, reflected by higher axillary lymph node invasion and distant metastasis, as well as the largest concentrations of cathepsin D. An important aspect is cathepsin D, a protease with important biological functions and involved in invasion -metastatización of mammary tumors [37-40]. We know that correlates with cell proliferation and histological grade III, and that age can influence their associations with hormone dependence [41]. Our results suggest that it is from one cm in size when is evidenced in invasive ductal breast carcinomas certain clinical and biological properties source of increased proliferation and tumor aggressiveness.

REFERENCES

 

  1. Orucevic A, Chen J, McLoughlin JM, Heidel RE, Panella T, Bell J, et al. Is the TNM staging system for breast cancer still relevant in the era of biomarkers and emerging personalized medicine for breast cancer - an insti. Breast J. 2015; 21: 147-154.
  2. Yip CH, Taib NA, Tan GH, Ng KL, Yoong BK, Choo WY, et al. Predictors of axillary lymph node metastases in breast cancer: is there a role for minimal axillary surgery. World J Surg. 2009; 33: 54-57.
  3. Wang Z, Zhou Q, Liu J, Tang S, Liang X, Zhou Z, et al. Tumor size of breast invasive ductal cancer measured with contrast-enhanced ultrasound predicts regional lymph node metastasis and N stage. Int J Clin Exp Pathol. 2014; 7: 6985-6991.
  4. Saadatmand S, Bretveld R, Siesling S, Tilanus-Linthorst MM. Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173,797 patients. BMJ. 2015; 351: 4901.
  5. Fei F, Messina C, Slaets L, Chakiba C, Cameron D, Bogaerts J, et al. Tumour size is the only predictive factor of distant recurrence after pathological complete response to neoadjuvant chemotherapy in patients with l. Eur J Cancer. 2015; 51: 301-309.
  6. Hanrahan EO, Valero V, Gonzalez-Angulo AM, Hortobagyi GN. Prognosis and management of patients with node-negative invasive breast carcinoma that is 1 cm or smaller in size (stage 1; T1a,bN0M0): a review of... J Clin Oncol. 2006; 24: 2113-2122.
  7. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248-254.
  8. García JF, Camacho FI, Morente M, Fraga M, Montalbán C, Alvaro T, et al. Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microa. Blood. 2003; 101: 681-689.
  9. Bustreo S, Osella-Abate S, Cassoni P, Donadio M, Airoldi M, Pedani F, et al. Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: a large case series study with a long-term follow-up. Breast Cancer Res Treat. 2016; 157: 363-371.
  10. Madani SH, Payandeh M, Sadeghi M, Motamed H, Sadeghi E. The correlation between Ki-67 with other prognostic factors in breast cancer: A study in Iranian patients. Indian J Med Paediatr Oncol. 2016; 37: 95-99.
  11. Shandiz FH, Shabahang H, Afzaljavan F, Sharifi N, Tavasoli A, Afzalaghaee M, et al. Ki67 Frequency in Breast Cancers without Axillary Lymph Node Involvement and its Relation with Disease-free Survival. Asian Pac J Cancer Prev. 2016; 17: 1347-1350.
  12. Parsa Y, Mirmalek SA, Kani FE, Aidun A, Salimi-Tabatabaee SA, Yadollah-Damavandi S, et al. A Review of the Clinical Implications of Breast Cancer Biology. Electron Physician. 2016; 8: 2416-2424.
  13. Kim JY, Park K, Kang G, Kim HJ, Gwak G, Shin YJ, et al. Predictors of Recurrent Ductal Carcinoma In Situ after Breast-Conserving Surgery. J Breast Cancer. 2016; 19: 185-190.
  14. Dmitrenko AP. Lateral differences in Ki-67 in breast cancer. Mol Clin Oncol. 2016; 4: 1041-1044.
  15. Rachna, Rai MK. The Er/Ki-67 Proportion in Breast Tumours - An Immunohistochemical Study. J Clin Diagn Res. 2016; 10: EC06-EC09.
  16. Ruibal A, Núñez M, Tejerina A. Hyaluronic acid concentrations in cell membranes are inversely proportional to histological grade and ploidy in infiltrating ductal carcinoma of t. Rev Esp Med Nucl. 1998; 17: 310-311.
  17. Ruibal A, Arias JI, Del Río MC, Lapeña G, Schneider J, Tejerina A, et al. Histological grade in breast cancer: association with clinical and biological features in a series of 229 patients. Int J Biol Markers. 2001; 16: 56-61.
  18. Jiang H, Zhao W, Shao W. Prognostic value of CD44 and CD44v6 expression in patients with non-small cell lung cancer: meta-analysis. Tumour Biol. 2014; 35: 7383-7389.
  19. Prochazka L, Tesarik R, Turanek J. Regulation of alternative splicing of CD44 in cancer. Cell Signal. 2014; 26: 2234-2239.
  20. Chow G, Tauler J, Mulshine JL. Cytokines and growth factors stimulate hyaluronan production: role of hyaluronan in epithelial to mesenchymal-like transition in non-small cell lun. J Biomed Biotechnol. 2010; 2010: 485468.
  21. Basakran NS. CD44 as a potential diagnostic tumor marker. Saudi Med J. 2015; 36: 273-279.
  22. Paulis YW, Huijbers EJ, van der Schaft DW, Soetekouw PM, et al. CD44 enhances tumor aggressiveness by promoting tumor cell plasticity. Oncotarget. 2015; 6:19634-19646.
  23. Nuñez MI, Arias JI, Del Rio MC, Martinez MI, Alba A, Allende MT, et al. CD44v5 cell surface levels in infiltrating ductal carcinomas of the breast. First results. Rev Senoloñga y Pat Mam. 1997; 10:175-180.
  24. Loh TJ, Moon H, Cho S, Jang H, Liu YC, Tai H2, et al. CD44 alternative splicing and hnRNP A1 expression are associated with the metastasis of breast cancer. Oncol Rep. 2015; 34: 1231-1238.
  25. Nuñez MI, Arias JI, Del Rio MC, Martinez MI, Alba A, Allende MT, et al. Cell surface CD44v5 levels correlate with progesterone receptors and a tumor size > 2 cm in infiltrating ductal carcinomas of the breast. Int J Biol Markers. 1996; 11: 220-222.
  26. Berner HS, Nesland JM. Expression of CD44 isoforms in infiltrating lobular carcinoma of the breast. Breast Cancer Res Treat. 2001; 65: 23-29.
  27. Kittl EM, Ruckser R, Selleny S, Samek V, Hofmann J, Huber K, et al. Evaluation of soluble CD44 splice variant v5 in the diagnosis and follow-up in breast cancer patients. Exp Clin Immunogenet. 1997; 14: 264-72.
  28. Wu XJ, Li XD, Zhang H, Zhang X, Ning ZH, Yin YM, et al. Clinical significance of CD44s, CD44v3 and CD44v6 in breast cancer. J Int Med Res. 2015; 43: 173-179.
  29. Ormenisan C, Kubik M, Legrand S, Kraemer D, Smotherman C, Masood S. The potential of ki67 and p53 assessment in development of individualized targeted therapy in breast cancer patients. Pathologica. 2015; 107: 177-180.
  30. Fountzilas G, Giannoulatou E, Alexopoulou Z, Zagouri F, Timotheadou E, Papadopoulou K, et al. TP53 mutations and protein immunopositivity may predict for poor outcome but also for trastuzumab benefit in patients with early breast cancer trea. Oncotarget. 2016; 7: 32731-32753.
  31. Ohara M, Matsuura K, Akimoto E, Noma M, Doi M, Nishizaka T. et al. Prognosticvalue of Ki67 and p53 in patientswithestrogen receptor-positive and human epidermalgrowth factor receptor 2-negative breastcancer: Validation of thecut-off value of the Ki67 labelingindex as a predictive factor. Mol Clin Oncol. 2016;4:648-654.
  32. Ruibal Á, Aguiar P, Del Río MC, Menéndez P, Arias JI, Herranz M, et al. Positive immunohistochemical expression of bcl-2 in hormone-independent breast carcinomas is associated with a greater lymph node involvement and p. Med Oncol. 2014; 3:105.
  33. Bouchalova K, Svoboda M, Kharaishvili G, Vrbkova J, Bouchal J, Trojanec R, et al. BCL2 is an independent predictor of outcome in basal-like triple-negative breast cancers treated with adjuvant anthracycline-based chemotherapy. Tumour Biol. 2015; 36: 4243-4252.
  34. Ruibal Á, Aguiar P, Del Rio MC, Arias JI, Menéndez-Rodríguez P, Gude F, et al. Histological grade (HG) in invasive ductal carcinomas of the breast of less than 1 cm: clinical and biological associations during progression from Anticancer Res. 2015; 35: 569-573.
  35. Chen LY, Tsang JY, Ni YB, Chan SK, Chan KF, Zhang S, et al. Bcl2 and Ki67 refine prognostication in luminal breast cancers. Breast Cancer Res Treat. 2015; 149: 631-643.
  36. Min KW, Kim DH, Do SI, Pyo JS, Chae SW, Sohn JH, et al. High Ki67/BCL2 index is associated with worse outcome in early stage breast cancer. Postgrad Med J. 2016; 2015: 133531.
  37. Dian D, Heublein S, Wiest I, Barthell L, Friese K, Jeschke U. Significance of the tumor protease cathepsin D for the biology of breast cancer. Histol Histopathol. 2014; 29: 433-438.
  38. Maynadier M, Farnoud R, Lamy PJ, Laurent-Matha V, Garcia M, Rochefort H, et al. Cathepsin D stimulates the activities of secreted plasminogen activators in the breast cancer acidic environment. Int J Oncol. 2013; 43: 1683-1690.
  39. Foekens JA, Look MP, Bolt-de Vries J, Meijer-van Gelder ME, van Putten WL, et al. Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients. Br J Cancer. 1999; 79: 300-307.
  40. Marki?evi? M, Kanjer K, Manduši? V, Buta M, Neškovi?-Konstantinovi? Z, Nikoli?-Vukosavljevi? D, et al. Cathepsin D as an indicator of clinical outcome in early breast carcinoma during the first 3 years of follow-up. Biomark Med. 2013; 7: 747-758.
  41. Ruibal A Herranz M, Arias JI. Clinical and Biological Significance of Cathepsin D Levels in Breast Cancer Cytosol in Women Over 70 years. Biomark Cancer. 2012; 4: 1-6.

Ruibal A, Aguiar P, Arias JI, Herranz M (2016) Size In Breast Invasive Ductal Carcinoma Leads Changes in Important Biological Parameters. JSM Surg Oncol Res 1(2): 1006.

Received : 18 Jan 2038
Accepted : 03 Oct 2016
Published : 18 Jan 2038
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X